Pregnancy and Lactation pdf - Endocrinology and Reproduction

fallopian tubes soon after both the sperm and the ovum enter the ampulla. But

Fertilization of the ovum normally takes place in the ampulla of one of the

billion sperm deposited in the vagina, a few thousand succeed in reaching each

posterior pituitary gland of the female during her orgasm. Of the almost half a

fallopian tubes near the ovarian ends of the tubes. This transport of the sperm

intercourse, a few sperm are transported within 5 to 10 minutes upward from

the opposite fallopian tube.

with relative ease of conception, thus demonstrating that ova can even enter

succeed in this task. Indeed, in some recorded cases, women with one ovary

on the basis of conception studies, it is probable that as many as 98 per cent

It seems likely that many ova might fail to enter the fallopian tubes. However,

one of the fallopian tubes.

slow fluid current flowing toward the ostium. By this means, the ovum enters

of the involved fallopian tube. One can actually see a

the opening, or

are activated by estrogen from the ovaries, which causes the cilia to beat toward

faces of the fimbriated tentacles are lined with ciliated epithelium, and the

ated ends of each fallopian tube fall naturally around the ovaries. The inner sur-

enter one of the fallopian tubes to reach the cavity of the uterus. The fimbri-

When ovulation occurs, the ovum,

Entry of the Ovum into the Fallopian Tube (Oviduct).

end of one of the fallopian tubes.

into the abdominal cavity. Then, almost immediately, it enters the fimbriated

It is at this time that the ovum, still in the secondary oocyte stage, is ovulated

chromosomes in the secondary oocyte.

that is expelled. This leaves 23

somes loses one of its partners, which becomes incorporated in a

In this process, each of the 23 pairs of chromo-

secondary oocyte.

is expelled from the nucleus of the oocyte. The primary oocyte then

it is released from the ovarian follicle, its nucleus divides by meiosis and a

stage. Shortly before

While still in the ovary, the ovum is in the

Maturation and Fertilization of the Ovum

discuss the physiology of pregnancy. In Chapter 83, some special aspects of fetal

eventually develops into a full-term fetus. The

takes place, and the fertilized ovum

pregnancy,

fertilized, a new sequence of events called

fertilization of the ovum. If the ovum becomes

In Chapters 80 and 81, the sexual functions of the

Pregnancy and Lactation

1027

male and female are described to the point of

gestation,

purpose of this chapter is to discuss the early stages
of ovum development after fertilization and then to

and early childhood physiology are discussed.

primary oocyte

first

polar body
becomes the

polar body

unpaired

along with a hundred or more attached granulosa cells that constitute the
corona radiata, is expelled directly into the peritoneal cavity and must then

cilia

ostium,

removed and the opposite fallopian tube removed have had several children

Fertilization of the Ovum.

After the male ejaculates semen into the vagina during

the vagina and through the uterus and fallopian tubes to the ampullae of the

is aided by contractions of the uterus and fallopian tubes stimulated by
prostaglandins in the male seminal fluid and also by oxytocin released from the

ampulla.

This delayed transport of the fertilized ovum

into the uterus.

then the progesterone activates the receptors, exerting

first 3 days after ovulation. After this time, the rapidly

fluid current. Also, the

The fallopian tubes are lined with a rugged, cryptoid

fallopian tube may also aid the ovum passage.

beat toward the uterus. Weak contractions of the

ciliated epithelium that lines the tube; the cilia always

the cavity of the uterus (Figure 82–2). This transport is

After fertilization has occurred, an additional 3 to 5

in the Fallopian Tube

Transport of the Fertilized Ovum

some from an ovum, giving an XY combination, a male

be born, as explained in Chapter 80. But if a Y chro-

ovum, giving an XX combination, a female child will

chromosome). Therefore, if an X chromosome from

some) and half carry a Y chromosome (the male

formation of the mature sperm, half of these carry in

(see Figure 82–1

ovum

fertilized

. Later, the

shown in Figure 82–1

male pronucleus,

changed. On entering the ovum, its head swells to form

In the meantime, the fertilizing sperm has also

chromosome.

somes is the female chromosome, known as the

) 23 chromosomes. One of these chromo-

that is expelled. The mature

mature ovum

oocyte divides again to form the

in the secondary oocyte stage of development), the

the ovum itself. The mechanisms used by the sperm for

zona pellucida

before a sperm can enter the ovum, it must first pene-

1028

Unit XIV

Endocrinology and Reproduction

trate the multiple layers of granulosa cells attached to
the outside of the ovum (the corona radiata) and then
bind to and penetrate the

surrounding

these purposes are presented in Chapter 80.

Once a sperm has entered the ovum (which is still

plus

a second polar body
ovum still carries in its nucleus (now called the female
pronucleus

23 unpaired chromosomes of the male pronucleus and
the 23 unpaired chromosomes of the female pronu-
cleus align themselves to re-form a complete comple-
ment of 46 chromosomes (23 pairs) in the

E).

What Determines the Sex of the Fetus That Is Created?

After

their genome an X chromosome (the female chromo-

a sperm combines with an X chromosome from an

mosome from a sperm is paired with an X chromo-

child will be born.

days is normally required for transport of the fertilized
ovum through the remainder of the fallopian tube into

effected mainly by a feeble fluid current in the tube
resulting from epithelial secretion plus action of the

surface that impedes passage of the ovum despite the

isthmus of the fallopian tube

(the last 2 centimeters before the tube enters the
uterus) remains spastically contracted for about the

increasing progesterone secreted by the ovarian
corpus luteum first promotes increasing progesterone
receptors on the fallopian tube smooth muscle cells;

a tubular relaxing effect that allows entry of the ovum

through the fallopian tube allows several stages of cell
division to occur before the dividing ovum—now
called a blastocyst, with about 100 cells—enters the

Corona

radiata

Sperm

Female
pronucleus

Centrosome

Sperm

Male
pronucleus

Dispersed corona radiata

Anatomy: A Textbook and Laboratory Manual of Embryology, 7th

division of the ovum. (Modified from Arey LB: Developmental

ganization of a full complement of chromosomes and beginning

Formation of the male and female pronuclei.

sperm.

Entry of the

Dispersal of the corona radiata.

corona radiata.

The mature ovum surrounded by the

Fertilization of the ovum.

Figure 82–1

E, Reor-

ed. Philadelphia: WB Saunders, 1974.)

Fertilization

(day 1)

Cell division

Fallopian

tube

Ovary

Ovum

Ovulation

Zygote

Blastocyst

reaches

uterus

(days 4-5)

Blastocyst

implants

(days 5-7)

Uterus

Amniotic
cavity

Trophoblastic
cells invading
endometrium

Action of tro-

Ovulation, fertilization of the ovum in the fallopian tube, and

Figure 82–2

A,
implantation of the blastocyst in the uterus. B,
phoblast cells in implantation of the blastocyst in the uterine
endometrium.

and more projections, which become

phoblastic cords. The trophoblast cells send out more

Simultaneously,

begins to be pumped by the heart of the embryo itself.

embryo. By the 16th day after fertilization, blood also

attaching to the uterus, blood capillaries grow into the

While the trophoblastic cords from the blastocyst are

Anatomy of the Placenta

phoblastic period of nutrition, which gradually gives

week after implantation). Figure 82–4 shows this tro-

nutrition in this way for up to 8 weeks, although the

During the first week after implantation, this is the

ing and imbibing it, the stored nutrients in the decidua

As the trophoblast cells invade the decidua, digest-

decidual cells,

and to store even more nutrients. These cells are now

the endometrium, the continued secretion of proges-

the conceptus. Then, when the conceptus implants in

taining extra quantities of glycogen, proteins, lipids,

effect on the uterine endometrium, converting the

latter half of each monthly sexual cycle has an

In Chapter 81, we pointed out that the progesterone

Early Nutrition of the Embryo

branes of pregnancy.

rapidly, forming the placenta and the various mem-

blastocyst and the uterine endometrium) proliferate

a small embryo. Once implantation has taken place,

82–3 shows an early implanted human blastocyst, with

tocyst, adding more sustenance for growth. Figure

These cells secrete proteolytic enzymes that digest and

that develop over the surface of the blastocyst.

endometrial secretions, called “uterine milk.”

the blastocyst obtains its nutrition from the uterine

seventh day after ovulation. Before implantation,

3 days before it implants in the endometrium; thus,

After reaching the uterus, the developing blastocyst

in the Uterus

Implantation of the Blastocyst

nutrition of the developing blastocyst.

uterus. During this time, the fallopian tube secretory

Chapter 82

Pregnancy and Lactation

1029

cells produce large quantities of secretions used for the

usually remains in the uterine cavity an additional 1 to

implantation ordinarily occurs on about the fifth to

Implantation results from the action of trophoblast

cells

liquefy the adjacent cells of the uterine endometrium.
Some of the fluid and nutrients released are actively
transported by the same trophoblast cells into the blas-

the trophoblast cells and other adjacent cells (from the

secreted by the ovarian corpus luteum during the

endometrial stromal cells into large swollen cells con-

and even some minerals necessary for development of

terone causes the endometrial cells to swell further

called

and the total mass of cells is called

the decidua.

are used by the embryo for growth and development.

only means by which the embryo can obtain nutrients;
the embryo continues to obtain at least some of its

placenta also begins to provide nutrition after about
the 16th day beyond fertilization (a little more than 1

way to placental nutrition.

Function of the Placenta

Developmental and Physiologic

cords from the vascular system of the newly forming

blood sinuses supplied with blood from

the mother develop around the outsides of the tro-

placental villi into

Trophoblasts

Ovum

Endometrium

Hertig.)

digestion and invasion of the endometrium. (Courtesy Dr. Arthur

Implantation of the early human embryo, showing trophoblastic

Figure 82–3

diffusion

Trophoblastic

12 16 20 24 28 32 36

Parturition

Ovulation

nutrition

Placental

100

Duration of pregnancy (weeks)

Placental membrane conductivity

(per cent of maximum)

diffusion through the placental membrane.

trial decidua, and essentially all the later nutrition results from

phoblastic digestion and absorption of nutrients from the endome-

Nutrition of the fetus. Most of the early nutrition is due to tro-

Figure 82–4

lung in Chapter 40, provides another mechanism to

Third, the

amount of oxygen transported to the fetal tissues.

Second, the

in fetal blood, the fetal hemoglobin can carry 20 to 50

nal hemoglobin. This means that at the low P

and fetal hemoglobin, demonstrating that the curve for

fetus before birth. Figure 82–6 shows the comparative

First, the hemoglobin of the fetus is mainly

mother’s blood to her tissues.

of only 30 mm Hg. There are

membrane is about 20 mm Hg.

is about 30 mm Hg. Therefore, the mean pressure gra-

sinuses is about 50 mm Hg, and the mean P

of the mother’s blood in the placental

blood to the fetus’s blood. Near the end of pregnancy,

by an oxygen pressure gradient from the mother’s

gen through the placental membrane. The dissolved

tured placental membrane.

severely into the mother’s circulation because of a rup-

the fetus. Fortunately, it is rare for the fetus to bleed

or, even less commonly, the mother’s cells to pass into

Rarely, “breaks” occur in the placental membrane,

Figure 82–4.

surface area expands many times over, thus giving the

nancy, the permeability increases because of thinning

ductance is minuscule at first. Conversely, in later preg-

grown significantly. Therefore, the total diffusion con-

oped. Therefore, its permeability is low. Further, the

In the early months of pregnancy, the placental

from the fetus back into the mother.

blood into the fetus’s blood and

from the mother’s

diffusion of foodstuffs and oxygen

The major function of the placenta is to provide for

Diffusion Conductance

Placental Permeability and Membrane

membranes elsewhere in the body.

ertheless, nutrients and other substances pass through

the area of the pulmonary membrane in the lungs. Nev-

The total surface area of all the villi of the mature pla-

the mother. The lower part of Figure 82–5 shows the

fetus. At the same time, the mother’s blood flows from

umbilical arteries,

82–5. Note that the fetus’s blood flows through two

The final structure of the placenta is shown in Figure

blood, are surrounded by sinuses that contain maternal

which fetal capillaries grow. Thus, the villi, carrying fetal

1030

Unit XIV

Endocrinology and Reproduction

blood.

then into the capillaries of the villi,

and finally back through a single umbilical vein into the

her uterine arteries into large maternal sinuses that sur-
round the villi and then back into the uterine veins of

relation between the fetal blood of each fetal placental
villus and the blood of the mother surrounding the out-
sides of the villus in the fully developed placenta.

centa is only a few square meters—many times less than

this placental membrane mainly by diffusion in much
the same manner that diffusion occurs through the
alveolar membranes of the lungs and the capillary

diffusion of excretory

products

membrane is still thick because it is not fully devel-

surface area is small because the placenta has not

of the membrane diffusion layers and because the

tremendous increase in placental diffusion shown in

which allows fetal blood cells to pass into the mother

Diffusion of Oxygen Through the Placental Membrane.

Almost the same principles for diffusion of oxygen
through the pulmonary membrane (discussed in detail
in Chapter 39) are applicable for diffusion of oxy-

oxygen in the blood of the large maternal sinuses
passes into the fetal blood by simple diffusion, driven

the mean P

in the

fetal blood after it becomes oxygenated in the placenta

dient for diffusion of oxygen through the placental

One might wonder how it is possible for a fetus to

obtain sufficient oxygen when the fetal blood leaving
the placenta has a P

three reasons why even this low P

is capable of

allowing the fetal blood to transport almost as much
oxygen to the fetal tissues as is transported by the

fetal

hemoglobin, a type of hemoglobin synthesized in the

oxygen dissociation curves for maternal hemoglobin

fetal hemoglobin is shifted to the left of that for mater-

levels

per cent more oxygen than maternal hemoglobin can.

hemoglobin concentration of fetal blood

is about 50 per cent greater than that of the mother; this
is an even more important factor in enhancing the

Bohr effect, which is explained in relation

to the exchange of carbon dioxide and oxygen in the

Villus

Maternal

vessels

Marginal

sinus

VILLUS

PLACENTA

Chorion

Amnion

Trophoblast

Umbilical arteries

Umbilical vein

Umbilical cord

Fetal capillaries

Intervillous space

Chorionic epithelium

Intravillus

space

Limiting layer

Stratum spongiosum

Placental septum

To the mother

From the mother

tory Manual of Embryology, 7th ed. Philadelphia: WB Saunders,

from Arey LB: Developmental Anatomy: A Textbook and Labora-

Human Body, 25th ed. Philadelphia: Lea & Febiger, 1948; and

villous spaces. (Modified from Gray H, Goss CM: Anatomy of the

fetal blood in the villus capillaries to the mother’s blood in the inter-

Below,

Organization of the mature placenta.

Figure 82–5

Above,

Relation of the

1974.)

pregnancy.

the fourth as well, are all essential to a normal

the first three of which, and probably

human chorionic somatomam-

progesterone,

human chorionic gonadotropin, estrogens,

In pregnancy, the placenta forms especially large

in Pregnancy

Hormonal Factors

of diffusion gradients across the placental membrane,

from the fetus occurs mainly, if not entirely, as a result

than that in the mother’s blood. Therefore, excretion

However, creatinine, which does not diffuse as easily,

fuses through the placental membrane with great ease.

greater than that in maternal blood, because urea dif-

The level of urea in fetal blood is only slightly

tinine.

urea, uric acid,

products of the mother. These include especially the

from the fetal blood into the maternal blood, other

Excretion of Waste Products Through the Placental Membrane.

and potassium, sodium, and chloride ions diffuse with

for nutrition. Also, such substances as ketone bodies

glucose, so that glucose is used more easily by the fetus

blood into the fetal blood, but more slowly than

membranes, these also diffuse from the maternal

cells of the membrane. Even so, the glucose level in

through the placental membrane. That is, the glucose

much glucose, the trophoblast cells lining the placen-

the entire body of the mother uses. To provide this

pregnancy, the fetus often uses as much glucose as

oxygen does. For instance, in the late stages of

Diffusion of Foodstuffs Through the Placental Membrane.

diffusion of carbon dioxide, because the extreme sol-

mm Hg higher than that of the maternal blood. This

mother’s blood. The P

tissues, and the only means for excreting the carbon

with that of the lungs of the newborn baby.

ference across the membrane.This compares favorably

The total

of only 30 mm Hg.

membrane, despite the fact that the fetal blood leaving

By these three means, the fetus is capable of receiv-

exchange in the lungs; therefore, it is called the

tion in the fetal blood. These two effects make the

the fetal blood. Thus, the Bohr shift operates in one

the maternal blood, while enhancing oxygen uptake by

blood to decrease. This forces still more oxygen from

These changes cause the capacity of fetal blood to

makes it more acidic.

dioxide makes the fetal blood more alkaline, whereas

blood into the maternal blood. Loss of the carbon

placenta carries large amounts of carbon dioxide, but

. The fetal blood entering the

is, hemoglobin can carry more oxygen at a low P

enhance the transport of oxygen by fetal blood. That

Chapter 82

Pregnancy and Lactation

1031

than it can at a high P

much of this carbon dioxide diffuses from the fetal

the increased carbon dioxide in the maternal blood

combine with oxygen to increase and that of maternal

direction in the maternal blood and in the other direc-

Bohr shift twice as important here as it is for oxygen

double

Bohr effect.

ing more than adequate oxygen through the placental

the placenta has a P

diffusing capacity of the entire placenta for

oxygen at term is about 1.2 milliliters of oxygen per
minute per millimeter of mercury oxygen pressure dif-

Diffusion of Carbon Dioxide Through the Placental Membrane.

Carbon dioxide is continually formed in the tissues of
the fetus in the same way that it is formed in maternal

dioxide from the fetus is through the placenta into the

of the fetal blood is 2 to 3

small pressure gradient for carbon dioxide across the
membrane is more than sufficient to allow adequate

ubility of carbon dioxide in the placental membrane
allows carbon dioxide to diffuse about 20 times as
rapidly as oxygen.

Other metabolic substrates needed by the fetus
diffuse into the fetal blood in the same manner as

tal villi provide for facilitated diffusion of glucose

is transported by carrier molecules in the trophoblast

fetal blood is 20 to 30 per cent lower than that in
maternal blood.

Because of the high solubility of fatty acids in cell

relative ease from the maternal blood into the fetal
blood.

In the same manner that carbon dioxide diffuses

excretory products formed in the fetus also diffuse
through the placental membrane into the maternal
blood and are then excreted along with the excretory

nonprotein nitrogens such as

and crea-

has a fetal blood concentration considerably higher

because there are higher concentrations of the excre-
tory products in the fetal blood than in the maternal
blood.

quantities of

and

motropin,

100

Fetal

Maternal

Human

100

(mm Hg)

Oxyhemoglobin (per cent)

Fed Proc 23:775, 1964.)

Metcalfe J, Moll W, Bartels H: Gas exchange across the placenta.

. (Data from

oxygen than can maternal blood for a given blood P

blood, showing that fetal blood can carry a greater quantity of

Oxygen-hemoglobin dissociation curves for maternal and fetal

Figure 82–6

estrogens and progesterone. Histochemical and

The placenta, like the corpus luteum, secretes both

organs. Near the end of pregnancy, the testosterone

in male fetuses until the time of birth. This small secre-

male fetus, resulting in the production of testosterone

Testes.

Effect of Human Chorionic Gonadotropin on the Fetal

period. The corpus luteum involutes slowly after the

maintain pregnancy for the remainder of the gestation

the 12th week. After that time, the placenta secretes

abortion almost always occurs, sometimes even up to

mately the 7th week of pregnancy, spontaneous

for the early development of the fetus.

nature of the uterine endometrium, which is necessary

after pregnancy begins, and its continued secretion of

gonadotropin, the corpus luteum in the mother’s ovary

blastocyst implants.

sexual cycle become actual

menstruum. As a result, the

terone and estrogens—for the next few months. These

cycle. Instead, it causes the corpus luteum to secrete

hormone secreted by the pituitary gland. By far, its

der of pregnancy.

16 to 20 weeks. It continues at this level for the remain-

of pregnancy and decreases back to a lower value by

the endometrium. Then the rate of secretion rises

after ovulation, shortly after the blastocyst implants in

mother, as shown in Figure 82–7. The secretion of this

the syncytial trophoblast cells into the fluids of the

human chorionic gonadotropin

phoblast cells from the early fertilized ovum, the

tissues in the following manner.

the pregnancy would terminate. However, this is

from the uterine wall and is expelled to the exterior.

woman about 14 days after ovulation, at which time

to Prevent Menstruation

of the Corpus Luteum and

1032

Unit XIV

Endocrinology and Reproduction

Human Chorionic Gonadotropin
and Its Effect to Cause Persistence

Menstruation normally occurs in a nonpregnant

most of the endometrium of the uterus sloughs away

If this should happen after an ovum has implanted,

prevented by the secretion of human chorionic
gonadotropin by the newly developing embryonic

Coincidental with the development of the tro-

hormone

is secreted by

hormone can first be measured in the blood 8 to 9 days

rapidly to reach a maximum at about 10 to 12 weeks

Function of Human Chorionic Gonadotropin.

Human

chorionic gonadotropin is a glycoprotein having a
molecular weight of about 39,000 and much the
same molecular structure and function as luteinizing

most important function is to prevent involution of the
corpus luteum at the end of the monthly female sexual

even larger quantities of its sex hormones—proges-

sex hormones prevent menstruation and cause the
endometrium to continue to grow and store large

amounts of nutrients rather than being shed in the

decidua-like cells that

develop in the endometrium during the normal female

decidual cells—greatly

swollen and nutritious—at about the time that the

Under the influence of human chorionic

grows to about twice its initial size by a month or so

estrogens and progesterone maintains the decidual

If the corpus luteum is removed before approxi-

sufficient quantities of progesterone and estrogens to

13th to 17th week of gestation.

Human chorionic gonadotropin also exerts an

interstitial cell–stimulating effect on the testes of the

tion of testosterone during gestation is what causes the
fetus to grow male sex organs instead of female

secreted by the fetal testes also causes the testes to
descend into the scrotum.

Secretion of Estrogens
by the Placenta

Human chorionic
gonadotropin

Progesterone

Estrogens

Ovulation

24
22
20
18
16
14

12
10
8

6
4

300

200

100

120

100

Duration of pregnancy (weeks)

Human chorionic gonadotropin (IU/mL)

Estrogens (mg/24 hr estradiol equivalent)

Progesterone (mg/24 hr)

Parturition

of pregnancy.

gonadotropin at different stages

and progesterone, and con-

Rates of secretion of estrogens

Figure 82–7

centration of human chorionic

both the mother and the fetus.

during pregnancy. Therefore, it appears that human

native source of energy for the mother’s metabolism

the fat stores of the mother, thus providing this alter-

of such a hormonal effect is obvious. Further, the

fetus to energize its growth, the possible importance

larger quantities of glucose available to the fetus.

lization of glucose in the mother, thereby making

Third,

human chorionic somatomammotropin

growth hormone, but 100 times as much human

does. It also has a chemical structure similar to that of

those of growth hormone, causing the formation of

Second, this hormone has weak actions similar to

prolactin. However, attempts to promote lactation in

covered, it was first named

causes at least partial development of the animal’s

animals,

human chorionic somatomammotropin

First, when administered to several types of lower

important effects.

nancy hormones combined. It has several possible

somatomammotropin are uncertain, it is secreted in

the placenta. Although the functions of chorionic

of pregnancy in direct proportion to the weight of

fifth week of pregnancy. Secretion of this hormone

protein with a molecular weight of about 38,000, and

human chorionic somatomammotropin.

lactation, which is discussed later in this chapter.

the estrogen prepare the mother’s breasts for

4. The progesterone secreted during pregnancy helps

the early developing embryo.

There is also reason to

mother’s fallopian tubes and uterus to provide

the conceptus even before implantation, because

3. Progesterone contributes to the development of

of the pregnant uterus, thus preventing uterine

2. Progesterone decreases the contractility

embryo.

in the uterine endometrium, and these cells play

1. Progesterone causes decidual cells to develop

tial for the normal progression of pregnancy are as

The special effects of progesterone that are essen-

course of pregnancy, as shown in Figure 82–7.

placenta, averaging about a 10-fold increase during the

by the corpus luteum at the beginning of pregnancy, it

pregnancy—in fact, it is just as important as estrogen.

by the Placenta

embryo.

of fetal development during pregnancy, for example,

through the birth canal. There is much reason to

elastic. These changes allow easier passage of the fetus

of the mother, so that the sacroiliac joints become

The estrogens also relax the pelvic ligaments

mother’s female external genitalia.

breast ductal structure, and (3) enlargement of the

enlargement of the mother’s breasts and growth of the

cause (1) enlargement of the mother’s uterus, (2)

During pregnancy, the extreme quantities of estrogens

reproductive and associated organs of the mother.

estrogens in Chapter 81, we pointed out that these hor-

Function of Estrogen in Pregnancy.

pregnancy.)

fetal zone,

large, and about 80 per cent consists of a so-called

(The cortices of the fetal adrenal glands are extremely

the trophoblast cells into estradiol, estrone, and estriol.

glands of the fetus. These weak androgens are trans-

both in the mother’s adrenal glands and in the adrenal

hydroxydehydroepiandrosterone,

compounds,

basic substrates in the placenta. Instead, they are

the ovaries. Most important, the estrogens secreted

of production. However, the secretion of estrogens

creases to about 30 times the mother’s normal level

Figure 82–7 shows that toward the end of pregnancy,

like most other placental hormones, are secreted by

physiological studies show that these two hormones,

Chapter 82

Pregnancy and Lactation

1033

the syncytial trophoblast cells of the placenta.

the daily production of placental estrogens in-

by the placenta is quite different from secretion by

by the placenta are not synthesized de novo from

formed almost entirely from androgenic steroid

dehydroepiandrosterone and 16-

which are formed

ported by the blood to the placenta and converted by

the primary function of which seems to

be to secrete dehydroepiandrosterone during

In the discussions of

mones exert mainly a proliferative function on most

relatively limber and the symphysis pubis becomes

believe that estrogens also affect many general aspects

by affecting the rate of cell reproduction in the early

Secretion of Progesterone

Progesterone is also essential for a successful

In addition to being secreted in moderate quantities

is secreted later in tremendous quantities by the

follows:

an important role in the nutrition of the early

contractions from causing spontaneous
abortion.

it specifically increases the secretions of the

appropriate nutritive matter for the developing
morula and blastocyst.
believe that progesterone affects cell cleavage in

Human Chorionic
Somatomammotropin

A more recently discovered placental hormone is
called

It is a

it begins to be secreted by the placenta at about the

increases progressively throughout the remainder

quantities several times greater than all the other preg-

breasts and in some instances causes lactation.
Because this was the first function of the hormone dis-

human placental lactogen

and was believed to have functions similar to those of

humans with its use have not been successful.

protein tissues in the same way that growth hormone

chorionic somatomammotropin as growth hormone
is required to promote growth.

causes decreased insulin sensitivity and decreased uti-

Because glucose is the major substrate used by the

hormone promotes the release of free fatty acids from

chorionic somatomammotropin is a general metabolic
hormone that has specific nutritional implications for

iron, and the vitamins. For example, about 375 mil-

ciencies can occur, especially in calcium, phosphates,

a pregnant woman’s diet, a number of maternal defi-

normal storage depots of the mother.

these substances—some in the placenta, but most in the

extra needs, the mother’s body has already been storing

extra needs of the fetus. However, anticipating these

diet during the last months of pregnancy to supply these

ficient protein, calcium, phosphates, and iron from her

pregnancy. Ordinarily, the mother does not absorb suf-

the fetus occurs during the last trimester of pregnancy;

Nutrition During Pregnancy.

expended for muscle activity.

ing, greater amounts of energy than normal must be

heated. Also, owing to the extra load that she is carry-

a result, she frequently has sensations of becoming over-

about 15 per cent during the latter half of pregnancy. As

adrenocortical hormones, and the sex hormones, the

hormones during pregnancy, including thyroxine,

pounds.

priate prenatal control of diet, the mother’s weight gain

and partly because of hormonal factors. Without appro-

of food substrates from the mother’s blood by the fetus

increased desire for food, partly as a result of removal

During pregnancy, a woman often has a greatly

days after birth, that is, after loss of the fluid-retaining

remaining 3 pounds is generally fat accumulation. The

fluid in the blood and extracellular fluid, and the

increase of 9 pounds. About 6 pounds of this is extra

another 2 pounds, still leaving an average weight

The uterus increases about 2 pounds and the breasts

pounds is amniotic fluid, placenta, and fetal membranes.

two trimesters. Of this, about 7 pounds is fetus and 4

pounds, with most of this gain occurring during the last

The average weight gain during pregnancy is about 24

Weight Gain in the Pregnant Woman

edema, acne, and masculine or acromegalic features.

appearance, sometimes resulting in the development of

can cause marked changes in a pregnant woman’s

introitus opens more widely. Also, the various hormones

size. At the same time, the vagina enlarges and the

1100 grams, and the breasts approximately double in

instance, the uterus increases from about 50 grams to

is the increased size of the various sexual organs. For

to the fetus and to the excessive hormones of pregnancy

Body to Pregnancy

Response of the Mother’s

woman at the time of delivery.

cause relaxation of the pelvic ligaments. It has also been

probably played mainly by the estrogens, which also

bly even absent in pregnant women. Instead, this role is

estrous rat and guinea pig. This effect is weak or possi-

about 9000. This hormone, when injected, causes relax-

and progesterone.

of the ovary and by placental tissues. Its secretion is

hormone called relaxin, is secreted by the corpus luteum

substance besides the estrogens and progesterone, a

many times more calcium than the fetus does.

the baby’s birth, because the growing baby requires

to ossify its own bones. This secretion of parathyroid

ing normal calcium ion concentration in the mother’s

absorption from the mother’s bones, thereby maintain-

diet. Enlargement of these glands causes calcium

roid glands usually enlarge during pregnancy; this is

The mother’s parathy-

human chorionic thyrotropin,

hormone,

chorionic gonadotropin

ding amount. The increased thyroxine production is

ordinarily enlarges up to 50 per cent during pregnancy

The mother’s thyroid gland

tubules and, therefore, to retain fluid, occasionally

estrogens, causes a tendency for even a normal pregnant

at the end of gestation. This, along with the actions of

aldosterone,

in the fetus.

corticoids help mobilize amino acids from the mother’s

throughout pregnancy. It is possible that these gluco-

The rate of adrenocortical secre-

Conversely, pituitary secretion

corticotropin, thy-

mother enlarges at least 50 per cent during pregnancy

The anterior pituitary gland of the

Pituitary Secretion.

most notable effects are the following.

hormones on the pituitary and other glands. Some of the

but also, to some extent, from the effects of placental

mother also react markedly to pregnancy. This results

1034

Unit XIV

Endocrinology and Reproduction

Other Hormonal Factors
in Pregnancy

Almost all the nonsexual endocrine glands of the

mainly from the increased metabolic load on the mother

and increases its production of
rotropin, and prolactin.
of follicle-stimulating hormone and luteinizing
hormone is almost totally suppressed as a result of the
inhibitory effects of estrogens and progesterone from
the placenta.

Corticosteroid Secretion.

tion of the glucocorticoids is moderately increased

tissues so that these can be used for synthesis of tissues

Pregnant women usually have about a twofold

increase in the secretion of

reaching a peak

woman to reabsorb excess sodium from her renal

leading to pregnancy-induced hypertension.

Secretion by the Thyroid Gland.

and increases its production of thyroxine a correspon-

caused at least partly by a thyrotropic effect of human

secreted by the placenta and

by small quantities of a specific thyroid-stimulating

also secreted by

the placenta.

Secretion by the Parathyroid Glands.

especially true if the mother is on a calcium-deficient

extracellular fluid even while the fetus removes calcium

hormone is even more intensified during lactation after

Secretion of “Relaxin” by the Ovaries and Placenta.

Another

increased by a stimulating effect of human chorionic
gonadotropin at the same time that the corpus luteum
and the placenta secrete large quantities of estrogens

Relaxin is a polypeptide having a molecular weight of

ation of the ligaments of the symphysis pubis in the

claimed that relaxin softens the cervix of the pregnant

Most apparent among the many reactions of the mother

extra fluid is excreted in the urine during the first few

hormones from the placenta.

can be as great as 75 pounds instead of the usual 24

Metabolism During Pregnancy

As a consequence of the increased secretion of many

basal metabolic rate of the pregnant woman increases

By far the greatest growth of

its weight almost doubles during the last 2 months of

If appropriate nutritional elements are not present in

ligrams of iron is needed by the fetus to form its blood,
and an additional 600 milligrams is needed by the

occur in the normal pregnant woman. The renal effects

decreased, which is exactly opposite to the changes that

nificantly in the kidneys, brain, and liver. Both the renal

occurs in many parts of the mother’s body, most sig-

tion of the vascular endothelium, and arterial spasm

sion in the mother. In addition, there is impaired func-

salt and water retention by the mother’s kidneys and by

toxemia of pregnancy.

into the urine. This condition is called

levels during the last few months of pregnancy. This is

directly through the amniotic membranes.

turnover of the amniotic fluid is still present, which indi-

However, even after in utero death of a fetus, some

of the gastrointestinal tract and lungs of the fetus.

Likewise, a certain amount of absorption occurs by way

the fluid is derived from renal excretion by the fetus.

an average of once every 15 hours. A large portion of

water in amniotic fluid is replaced once every 3 hours,

formation of amniotic fluid show that, on average, the

as much as several liters. Isotope studies of the rate of

liliters and 1 liter, but it can be only a few milliliters or

Normally, the volume of

the urine. When all these effects are considered, the

much as 50 per cent during pregnancy, which tends to

Second, the glomerular filtration rate increases as

sodium, chloride, and water is increased as much as

First, the renal tubules’ reabsorptive capacity for

occur.

addition, several special alterations of urinary function

intake and increased load or excretory products. But in

The rate of urine formation by a pregnant woman is

Function of the Maternal Urinary System During Pregnancy

sion of the diaphragm is decreased. Consequently, the

upward against the diaphragm, so that the total excur-

upward against the abdominal contents, and these press

woman. Simultaneously, the growing uterus presses

respiratory center’s sensitivity to carbon dioxide. The

tion even more, because progesterone increases the

esterone during pregnancy increase the minute ventila-

increase. It is also believed that the high levels of prog-

These effects cause the mother’s minute ventilation to

birth of the baby is about 20 per cent above normal, and

nant woman and because of her greater size, the total

erable safety factor for the mother.

during delivery of the baby, thereby allowing a consid-

extra blood in her circulatory system. Only about one

birth of the baby, the mother has about 1 to 2 liters of

with the excess fluid volume. Therefore, at the time of

by the kidneys. Also, the bone marrow becomes increas-

increased in pregnancy, and to increased fluid retention

in part, to aldosterone and estrogens, which are greatly

The cause of the increased volume is likely due, at least

half of pregnancy, as shown by the curve of Figure 82–8.

normal. This increase occurs mainly during the latter

The maternal blood

Blood Volume During Pregnancy.

despite the high uterine blood flow.

above normal during the last 8 weeks of pregnancy,

unexplained, the cardiac output falls to only a little

normal by the 27th week of pregnancy; then, for reasons

the mother’s cardiac output to 30 to 40 per cent above

general increase in the mother’s metabolism, increases

during the last month of pregnancy. This, plus the

Pregnancy.

Blood Flow Through the Placenta, and Cardiac Output During

Changes in the Maternal Circulatory

hemorrhage, caused by the birth process.

thrombin to prevent hemorrhage, particularly brain

mother’s diet so that the baby will have sufficient pro-

birth of the baby, vitamin K is often added to the

testinal tract without vitamin D. Finally, shortly before

is normally poorly absorbed by the mother’s gastroin-

quantity of calcium used by the fetus is small, calcium

that she receive vitamin D, because although the total

. Also, it is especially important

hypochromic anemia

iron in her food, a pregnant woman usually develops

more than 700 milligrams. Therefore, without sufficient

pregnancy is often only 100 milligrams and almost never

mother to form her own extra blood. The normal store

Chapter 82

Pregnancy and Lactation

1035

of nonhemoglobin iron in the mother at the outset of

System During Pregnancy

About 625 milliliters of blood flows through

the maternal circulation of the placenta each minute

volume shortly before term is about 30 per cent above

ingly active and produces extra red blood cells to go

fourth of this amount is normally lost through bleeding

Maternal Respiration During Pregnancy

Because of the increased basal metabolic rate of a preg-

amount of oxygen used by the mother shortly before

a commensurate amount of carbon dioxide is formed.

net result is an increase in minute ventilation of about
50 per cent and a decrease in arterial P

to several

millimeters of mercury below that in a nonpregnant

respiratory rate is increased to maintain the extra
ventilation.

usually slightly increased because of increased fluid

50 per cent as a consequence of increased production
of steroid hormones by the placenta and adrenal
cortex.

increase the rate of water and electrolyte excretion in

normal pregnant woman ordinarily accumulates only
about 6 pounds of extra water and salt.

Amniotic Fluid and Its Formation

amniotic fluid (the fluid inside

the uterus in which the fetus floats) is between 500 mil-

and the electrolytes sodium and potassium are replaced

cates that some of the fluid is formed and absorbed

Preeclampsia and Eclampsia

About 5 per cent of all pregnant women experience a
rapid rise in arterial blood pressure to hypertensive

also associated with leakage of large amounts of protein

preeclampsia or

It is often characterized by excess

weight gain and development of edema and hyperten-

blood flow and the glomerular filtration rate are

12 16 20 24 28 32 36 40 44

Parturition

Duration of pregnancy (weeks)

Blood volume

(liters)

Effect of pregnancy to increase the mother’s blood volume.

Figure 82–8

tions. For instance, the obstetrician frequently induces

There is reason to

Stretch or Irritation of the Cervix.

stretch in eliciting uterine contractions.

child, which emphasizes the importance of mechanical

19 days

twins are born, on average,

elicit smooth muscle contraction. Note especially that

edly in the uterus because of fetal movements, can also

tility. Further, intermittent stretch, as occurs repeat-

Mechanical Factors That Increase

the intensity of uterine contractions.

centration at the time of labor. These, too, can increase

sol, another possible uterine stimulant. In addition, the

fetus’s adrenal glands secrete large quantities of corti-

which might play a role in exciting the uterus. Also, the

The fetus’s pitu-

occurs during labor, can cause a neurogenic reflex

that irritation or stretching of the uterine cervix, as

prolonged. (4) Experiments in animals indicate

animals can still deliver their young at term, labor is

at the time of labor. (3) Although hypophysectomized

months of pregnancy. (2) The rate of oxytocin secre-

receptors and, therefore, increases its responsiveness

term: (1) The uterine muscle increases its oxytocin

causes uterine contraction (see Chapter 75). There are

uterus.

toward the end of pregnancy to be at least partly

slightly. Therefore, it has been postulated that the

nancy, but from the seventh month onward, estrogen

also because of other poorly understood effects. Both

between the adjacent uterine smooth muscle cells, but

degree of uterine contractility,

partly because

estrogens have a definite tendency to increase the

helping to prevent expulsion of the fetus. Conversely,

inhibits uterine contractility during pregnancy, thereby

Hormonal Factors That Increase

(2) progressive mechanical changes.

increased excitability of the uterine musculature, and

tion: (1) progressive hormonal changes that cause

known, but at least two major categories of effects lead

cal contractions that the baby is expelled. The exact

excitable, until finally it develops such strong rhythmi-

pregnancy, the uterus becomes progressively more

means birth of the baby. Toward the end of

Parturition

Near Term

Parturition

mothers has been reduced to 1 per cent or less.

immediate termination of pregnancy—by cesarean

to reduce the arterial pressure to normal, followed by

centage of eclamptic mothers die. However, with optimal

before birth of the baby. Without treatment, a high per-

toxic condition of the body. It usually occurs shortly

the liver; often extreme hypertension; and a generalized

coma; greatly decreased kidney output; malfunction of

clonic seizures in the mother, sometimes followed by

tumor necrosis factor-

lial dysfunction are still uncertain, some experimental

increased blood pressure. Although the factors that link

flow to the kidneys, excess salt and water retention, and

impaired vascular endothelial function, decreased blood

stances that enter the mother’s circulation and cause

This, in turn, causes the placenta to release various sub-

these adaptive changes, for reasons that are still unclear,

preeclampsia, the maternal arterioles fail to undergo

with low resistance to blood flow. In patients with

placental development, the trophoblasts invade the

of the maternal vascular endothelium. During normal

resulting in the placenta’s

within a few days after birth of the baby. There is also

support of this, the acute symptoms usually disappear

in the mother caused by the presence of the fetus. In

basis is still lacking. Another theory is that preeclamp-

cental or adrenal hormones, but proof of a hormonal

Various attempts have been made to prove that

protein deposit in the basement membranes.

1036

Unit XIV

Endocrinology and Reproduction

also include thickened glomerular tufts that contain a

preeclampsia is caused by excessive secretion of pla-

sia results from some type of autoimmunity or allergy

evidence that preeclampsia is initiated by insufficient
blood supply to the placenta,
release of substances that cause widespread dysfunction

arterioles of the uterine endometrium and completely
remodel the maternal arterioles into large blood vessels

and there is insufficient blood supply to the placenta.

reduced placental blood supply with maternal endothe-

studies suggest a role for increased levels of inflamma-
tory cytokines such as

a and

interleukin-6.

Eclampsia is an extreme degree of preeclampsia,

characterized by vascular spasm throughout the body;

and immediate use of rapidly acting vasodilating drugs

section if necessary—the mortality even in eclamptic

Increased Uterine Excitability

cause of the increased activity of the uterus is not

up to the intense contractions responsible for parturi-

Uterine Contractility
Increased Ratio of Estrogens to Progesterone.

Progesterone

estrogens increase the number of gap junctions

progesterone and estrogen are secreted in progres-
sively greater quantities throughout most of preg-

secretion continues to increase while progesterone
secretion remains constant or perhaps even decreases

estrogen-to-progesterone ratio increases sufficiently

responsible for the increased contractility of the

Effect of Oxytocin on the Uterus.

Oxytocin is a hormone

secreted by the neurohypophysis that specifically

four reasons to believe that oxytocin might be impor-
tant in increasing the contractility of the uterus near

to a given dose of oxytocin during the latter few

tion by the neurohypophysis is considerably increased

through the paraventricular and supraoptic nuclei of
the hypothalamus that causes the posterior pituitary
gland (the neurohypophysis) to increase its secretion
of oxytocin.

Effect of Fetal Hormones on the Uterus.

itary gland secretes increasing quantities of oxytocin,

fetal membranes release prostaglandins in high con-

Uterine Contractility
Stretch of the Uterine Musculature.

Simply stretching

smooth muscle organs usually increases their contrac-

earlier than a single

believe that stretching or irritating the uterine cervix
is particularly important in eliciting uterine contrac-

labor by rupturing the membranes so that the head of

The uterine contractions during labor begin mainly at

Mechanics of Parturition

the baby.

contractions of these muscles. The abdominal contrac-

spinal cord to the abdominal muscles, causing intense

causing suffering, elicit neurogenic reflexes in the

and from the birth canal. These signals, in addition to

labor, pain signals originate both from the uterus itself

contractions would fade away.

back could go into a retrograde decline, and the labor

to re-excite the uterus sufficiently, the positive feed-

tive feedback must be stronger than the previous one.

new cycle of the posi-

each

vicious circle to continue,

stronger and then fade away. Remember that for a

labor, in which the contractions become stronger and

initiates a vicious circle when the gain of the feedback

because positive feedback

traction greater than the preceding one, the process

cause this type of feedback, with each succeeding con-

the first, a third stronger than the second, and so forth.

cially at the cervix, and this increases uterine

becomes strong enough to irritate the uterus, espe-

end of pregnancy. Eventually a uterine contraction

To summarize, we can assume that multiple factors

means for increasing uterine contractility.

pituitary gland to secrete oxytocin, which is another

baby’s head. (2) Cervical stretching also causes the

to contract, and this contraction stretches the cervix

increase uterine contractions during labor: (1) Stretch-

Second, two known types of positive feedback

a critical value.

positive feedback in control systems, one can see that

achieved. Referring to the discussion in Chapter 1 of

contraction becomes greater than a critical value, each

positive feedback. That is, once the strength of uterine

First, labor contractions obey all the principles of

porting it are the following.

is shown in Figure 82–9, and the observations sup-

process repeats until the baby is expelled. This theory

positive feedback to the uterine body. Thus, the

ity of the uterine body. This pushes the baby forward,

the cervix by the fetus’s head finally becomes great

positive feedback

been proposed for explaining the onset of labor. The

types of physiological control systems, a theory has

tractions. However, based on experience with other

We do not know what suddenly changes the slow,

labor contractions.

labor,

parturition. This process is called

force the baby through the birth canal, thereby causing

denly, within hours, to become exceptionally strong

toward the end of pregnancy; then they change sud-

These contractions become progressively stronger

Braxton Hicks contractions.

During most of the months of pregnancy, the uterus

Onset of Labor—A Positive Feedback

the uterus.

cervix initiates reflexes to the body of the uterus, but

the body of the uterus is not known. It has been

The mechanism by which cervical irritation excites

usual or irritates it in other ways.

Chapter 82

Pregnancy and Lactation

1037

the baby stretches the cervix more forcefully than

suggested that stretching or irritation of nerves in the

the effect could also result simply from myogenic
transmission of signals from the cervix to the body of

Mechanism for Its Initiation

undergoes periodic episodes of weak and slow rhyth-
mical contractions called

contractions that start stretching the cervix and later

and the strong

contractions that result in final parturition are called

weak rhythmicity of the uterus into strong labor con-

theory suggests that stretching of

enough to elicit a strong reflex increase in contractil-

which stretches the cervix more and initiates more

contraction leads to subsequent contractions that
become stronger and stronger until maximum effect is

this is the precise nature of all positive feedback mech-
anisms when the feedback gain becomes greater than

ing of the cervix causes the entire body of the uterus

even more because of the downward thrust of the

increase the contractility of the uterus toward the

contractility still more because of positive feedback,
resulting in a second uterine contraction stronger than

Once these contractions become strong enough to

proceeds to completion—all

is greater than a critical level.

One might ask about the many instances of false

If at any time after labor starts some contractions fail

Abdominal Muscle Contractions
During Labor

Once uterine contractions become strong during

tions add greatly to the force that causes expulsion of

the top of the uterine fundus and spread downward over

1. Baby's head stretches cervix
2. Cervical stretch excites fundic contraction
3. Fundic contraction pushes baby down and stretches
cervix some more
4. Cycle repeats over and over again

Theory for the onset of intensely strong contractions during labor.

Figure 82–9

in the development of the breasts.

metabolism, which presumably explains their function

adrenal glucocorticoids,

growth hormone, pro-

stroma of the breasts increases in quantity, and large

breasts to grow and branch. Simultaneously, the

through pregnancy, the large quantities of estrogens

estrogen state of pregnancy, and only then does the

addition, far greater growth occurs during the high-

plus the deposition of fat to give the breasts mass. In

estrogens of the monthly female sexual cycle; estro-

at puberty. This development is stimulated by the

The breasts, shown in Figure 82–10, begin to develop

ready for normal, nongravid sex life again.

continuing for a total of about 10 days. After this time,

“lochia,” which is first bloody and then serous in nature,

surface autolyzes, causing a vaginal discharge known as

of the uterus, the placental site on the endometrial

of lactation, as discussed later. During early involution

it was before pregnancy. This effect of lactation results

the mother lactates, the uterus may become as small as

ate postpartum weight within 1 week, and in 4 weeks, if

involutes. Its weight becomes less than half its immedi-

During the first 4 to 5 weeks after parturition, the uterus

instead of by the visceral sensory nerves.

mother’s spinal cord and brain by somatic nerves

in the vaginal canal itself. This pain is conducted to the

ineal stretching, and stretching or tearing of structures

more severe pain is caused by cervical stretching, per-

fetus is being expelled through the birth canal, much

However, during the second stage of labor, when the

sensory fibers leading from the uterus, have been

hypogastric nerves,

in the uterus. This pain is not felt when the visceral

considerable pain. The cramping pain in early labor

With each uterine contraction, the mother experiences

centa. In addition, it is believed that vasoconstrictor

through the uterine wall. Therefore, contraction of

liliters by the following mechanism: The smooth muscle

opens the placental sinuses and causes bleeding. The

from its implantation site. Separation of the placenta

the uterus and the placenta, thus separating the placenta

size, which causes a

For 10 to 45 minutes after birth of the baby, the

of the Placenta

pregnancy.

of labor,

until delivery is effected. This is called the

above, it continues to wedge its way through the canal

into the birth canal, and with additional force from

through the vagina. Then the fetus’s head moves rapidly

Once the cervix has dilated fully, the fetal membranes

many pregnancies.

the first pregnancy but often only a few minutes after

of the fetus. This stage usually lasts for 8 to 24 hours in

labor contractions begin in the uterus. The so-called

cervix becomes soft, which allows it to stretch when

is the uterine cervix. Toward the end of pregnancy, the

The first major obstruction to expulsion of the fetus

ing instances, the buttocks are presented first. The head

of the baby to be expelled, and in most of the remain-

In about 95 per cent of births, the head is the first part

death of the fetus.

stimulants, such as oxytocin, can cause uterine spasm

were continuous. Indeed, overuse of various uterine

intermittently, because strong contractions impede or

contractions. The combined contractions of the uterine

greatly, with only a short period of relaxation between

to 3 minutes, and the intensity of contraction increases

the contractions finally appear as often as once every 1

occur only once every 30 minutes. As labor progresses,

In the early part of labor, the contractions might

Therefore, each uterine contraction tends to force the

the body of the uterus. Also, the intensity of contraction

1038

Unit XIV

Endocrinology and Reproduction

is great in the top and body of the uterus but weak in
the lower segment of the uterus adjacent to the cervix.

baby downward toward the cervix.

and abdominal musculature during delivery of the baby
cause a downward force on the fetus of about 25 pounds
during each strong contraction.

It is fortunate that the contractions of labor occur

sometimes even stop blood flow through the placenta
and would cause death of the fetus if the contractions

rather than rhythmical contractions and can lead to

acts as a wedge to open the structures of the birth canal
as the fetus is forced downward.

first

stage of labor is a period of progressive cervical dilation,
lasting until the cervical opening is as large as the head

usually rupture and the amniotic fluid is lost suddenly

second stage

and it may last from as little as 1 minute after

many pregnancies to 30 minutes or more in the first

Separation and Delivery

uterus continues to contract to a smaller and smaller

shearing effect between the walls of

amount of bleeding is limited to an average of 350 mil-

fibers of the uterine musculature are arranged in figures
of eight around the blood vessels as the vessels pass

the uterus after delivery of the baby constricts the
vessels that had previously supplied blood to the pla-

prostaglandins formed at the placental separation site
cause additional blood vessel spasm.

Labor Pains

is probably caused mainly by hypoxia of the uterine
muscle resulting from compression of the blood vessels

sensory

which carry the visceral

sectioned.

Involution of the Uterus
After Parturition

from the suppression of pituitary gonadotropin and
ovarian hormone secretion during the first few months

the endometrial surface becomes re-epithelialized and

Lactation

Development of the Breasts

gens stimulate growth of the breasts’ mammary glands

glandular tissue become completely developed for the
production of milk.

Growth of the Ductal System—Role of the Estrogens.

All

secreted by the placenta cause the ductal system of the

quantities of fat are laid down in the stroma.

Also important for growth of the ductal system are

at least four other hormones:
lactin, the

and insulin. Each of

these is known to play at least some role in protein

The hypothal-

erably after 7 to 9 months.

several years if the child continues to suckle, although

or so. However, milk production can continue for

itary damage or if nursing does not continue, the

subsequent nursing periods. If this prolactin surge is

prolactin acts on the mother’s breasts to keep the

1 hour, which is also shown in Figure 82–11. This

each time the mother nurses her baby, nervous signals

next few weeks, as shown in Figure 82–11. However,

After birth of the baby, the

the amino acids, fatty acids, glucose, and calcium

These hormones are necessary to provide

growth hormone, cortisol, parathyroid hormone,

mother’s other hormones as well, but most important

instead of colostrum. This secretion of milk requires

promoting role, and over the next 1 to 7 days, the

the mother’s pituitary gland to assume its natural milk-

Immediately after the baby is born, the sudden loss

teins and lactose as milk, but it has almost no fat, and

The fluid secreted during the last few days before and

and progesterone, no more than a few milliliters of

Even so, because of the suppressive effects of estrogen

lactin from the mother’s pituitary during pregnancy.

bly has lactogenic properties, thus supporting the pro-

human chorionic somatomammotropin,

In addition, the placenta secretes large quantities of

end of pregnancy is shown in Figure 82–11.

nonpregnant level. This high level of prolactin at the

fifth week of pregnancy until birth of the baby, at

secreted by the mother’s anterior pituitary gland, and

on milk secretion—promoting it. This hormone is

Conversely, the

nancy, a specific effect of both these hormones is to

of Prolactin

menstrual cycle.

the alveoli. These changes are analogous to the

of the breast lobules, with budding of alveoli and

synergistically with estrogen, as well as with the other

ductal system has developed, progesterone—acting

progesterone.

Final development of the breasts into milk-

Chapter 82

Pregnancy and Lactation

1039

Development of the Lobule-Alveolar System—Role of Proges-
terone.

secreting organs also requires

Once the

hormones just mentioned—causes additional growth

development of secretory characteristics in the cells of

secretory effects of progesterone on the endometrium
of the uterus during the latter half of the female

Initiation of Lactation—Function

Although estrogen and progesterone are essential for
the physical development of the breasts during preg-

inhibit the actual secretion of milk.
hormone prolactin has exactly the opposite effect

its concentration in her blood rises steadily from the

which time it has risen to 10 to 20 times the normal

which proba-

fluid are secreted each day until after the baby is born.

the first few days after parturition is called colostrum;
it contains essentially the same concentrations of pro-

its maximum rate of production is about 1/100 the
subsequent rate of milk production.

of both estrogen and progesterone secretion from the
placenta allows the lactogenic effect of prolactin from

breasts begin to secrete copious quantities of milk

an adequate background secretion of most of the

are
and insulin.

required for milk formation.

basal level of prolactin

secretion returns to the nonpregnant level over the

from the nipples to the hypothalamus cause a 10- to
20-fold surge in prolactin secretion that lasts for about

mammary glands secreting milk into the alveoli for the

absent or blocked as a result of hypothalamic or pitu-

breasts lose their ability to produce milk within 1 week

the rate of milk formation normally decreases consid-

Hypothalamic Control of Prolactin Secretion.

amus plays an essential role in controlling prolactin

Pectoralis major

Adipose tissue

Lobules and
alveoli

Lactiferous
sinus (ampulla)

Lactiferous duct

Nipple

Areola

Ductule

Alveoli

Milk

secreting

epithelial

cells

Lobule

Myoepithelial cells

and milk-secreting cells of an alveolus

(milk ducts) that constitute its mammary gland

The breast and its secretory lobules, alveoli, and lactiferous ducts

Figure 82–10

(A). The enlarge-

ments show a lobule (B)
(C).

nervous system stimulation throughout the mother’s

that breast but also in the opposite breast. It is espe-

milk let-down.

milk ejection

begins to suckle, milk begins to flow. This process is

milk. Thus, within 30 seconds to 1 minute after a baby

baby’s suckling becomes effective in removing the

10 to 20 mm Hg. Then the

tract, thereby expressing the milk from the alveoli into

blood to the breasts, where it causes

cause prolactin secretion. The oxytocin is carried in the

oxytocin

hypothalamus, where they cause nerve signals that

nipples to the mother’s spinal cord and then to her

for the first half minute or so. Sensory impulses must

When the baby suckles, it receives virtually no milk

as follows.

oxytocin,

the baby can obtain it. This is caused by a combined

ually leak from the breast nipples. Instead, the milk

into the ductal system and, therefore, does not contin-

breasts, but milk does not flow easily from the alveoli

Milk Secretion—Function of Oxytocin

though nursing continues.

hormones to reinstate the monthly sexual cycle, even

those who nurse their babies only some of the time,

months of lactation, in some mothers, especially in

follicle-stimulating hormone. However, after several

mus. This, in turn, suppresses formation of the pituitary

until a few weeks after cessation of nursing. The reason

the ovarian cycle (and ovulation) does not resume

In most nursing mothers,

for Many Months After Delivery.

dopamine,

hormone.

gland. This factor is called

Therefore, it is believed that anterior pituitary secre-

anterior pituitary hormones.

prolactin production. Consequently, damage

production of all the other hormones, but it mainly

in one aspect: The hypothalamus mainly

pituitary hormones. However, this control is different

secretion, as it does for almost all the other anterior

1040

Unit XIV

Endocrinology and Reproduction

stimulates

inhibits
to the hypothalamus or blockage of the hypothalamic-
hypophysial portal system often increases prolactin
secretion while it depresses secretion of the other

tion of prolactin is controlled either entirely or almost
entirely by an inhibitory factor formed in the hypo-
thalamus and transported through the hypothalamic-
hypophysial portal system to the anterior pituitary

prolactin inhibitory

It is almost certainly the same as the cate-

cholamine

which is known to be secreted

by the arcuate nuclei of the hypothalamus and can
decrease prolactin secretion as much as 10-fold.

Suppression of the Female Ovarian Cycles in Nursing Mothers

seems to be that the same nervous signals from
the breasts to the hypothalamus that cause prolactin
secretion during suckling—either because of the
nervous signals themselves or because of a subsequent
effect of increased prolactin—inhibit secretion of
gonadotropin-releasing hormone by the hypothala-

gonadotropic hormones—luteinizing hormone and

the pituitary begins to secrete sufficient gonadotropic

Ejection (or “Let-Down”) Process in

Milk is secreted continuously into the alveoli of the

must be ejected from the alveoli into the ducts before

neurogenic and hormonal reflex that involves the
posterior pituitary hormone

first be transmitted through somatic nerves from the

promote

secretion at the same time that they

myoepithelial cells

(which surround the outer walls of the alveoli) to con-

the ducts at a pressure of

called

Suckling on one breast causes milk flow not only in

cially interesting that fondling of the baby by the
mother or hearing the baby crying often gives enough
of an emotional signal to the hypothalamus to cause
milk ejection.

Inhibition of Milk Ejection.

A particular problem in

nursing a baby comes from the fact that many psy-
chogenic factors or even generalized sympathetic

Weeks after parturition

Intermittent secretion

of prolactin during

nursing

Progesterone

Prolactin

Estrogens

Parturition

300

2.0

200

100

1.5

1.0

0.5

200

100

Progesterone (mg/24 hr)

Estrogens (mg/24 hr estradiol equivalent)

Prolactin (ng/mL)

time) during and after periods of

secretion (for about 1 hour at a

tent periods of marked prolactin

parturition, but also the intermit-

prolactin secretion back to basal

Note especially the decrease of

turition and 36 weeks thereafter.

prolactin for 8 weeks before par-

of estrogens, progesterone, and

Changes in rates of secretion

Figure 82–11

levels within a few weeks after

nursing.

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differentiation. N Engl J Med 350:367, 2004.

MacLaughlin DT, Donahoe PK: Sex determination and

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Labbok MH, Clark D, Goldman AS: Breastfeeding: main-

models.Am J Physiol Regul Integr Comp Physiol 283:R29,

arterial pressure in preeclampsia: lessons from animal

Khalil RA, Granger JP: Vascular mechanisms of increased

327:610, 2003.

Khalaf Y: ABC of subfertility: tubal subfertility. BMJ

ine growth retardation. Ann N Y Acad Sci 997:150, 2003.

Kanaka-Gantenbein C, Mastorakos G, Chrousos GP:

Hall JG: Twinning. Lancet 362:735, 2003.

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Preeclampsia: linking placental ischemia with cardiovas-

Alexander BT, Bennett WA, Khalil RA, Granger JP:

environment of the human being.

baby in place of mother’s milk, the protective agents

When cow’s milk is used to supply nutrition for the

rhea in newborns.

bacteria, which often cause lethal diar-

Escherichia coli

infections in newborn babies. Particularly important

macrophages,

types of white blood cells are secreted, including both

milk along with the nutrients. Also, several different

against infection. For instance, multiple types of

nutrients, but it also provides important protection

big problem during pregnancy, but it can become more

fied. The mother’s bone decalcification is usually not a

greatly, and the bones become progressively decalci-

calcium and phosphate, the parathyroid glands enlarge

the intake of these substances. To supply the needed

of vitamin D, the output of calcium and phosphate by

phate may be lost each day; unless the mother is drink-

mother’s glucose. Also, 2 to 3 grams of calcium phos-

lactose, which must be derived by conversion from the

enter the milk each day, and about 100 grams of

from the mother. For instance, about 50 grams of fat

if the mother has twins). With this degree of lactation,

At the height of lactation in the human mother, 1.5

cow’s milk.

other minerals, is found in human milk compared with

one third as much ash, which contains calcium and

or more times greater than in human milk. Finally, only

concentration of protein in cow’s milk is ordinarily two

about 50 per cent greater than in cow’s milk, but the

milk. The concentration of lactose in human milk is

Table 82–1 lists the contents of human milk and cow’s

Caused by Lactation

Metabolic Drain on the Mother

Milk Composition and the

successful in nursing their babies.

depress milk ejection. For this reason, many mothers

Chapter 82

Pregnancy and Lactation

1041

body can inhibit oxytocin secretion and consequently

must have an undisturbed puerperium if they are to be

liters of milk may be formed each day (and even more

great quantities of metabolic substrates are drained

ing large quantities of milk and has an adequate intake

the lactating mammae will often be much greater than

important during lactation.

Antibodies and Other Anti-infectious Agents in Milk.

Not only

does milk provide the newborn baby with needed

anti-

bodies and other anti-infectious agents are secreted in

neutrophils and

some of which are

especially lethal to bacteria that could cause deadly

are antibodies and macrophages that destroy

in it are usually of little value because they are
normally destroyed within minutes in the internal

References

Endocrine-related causes and consequences of intrauter-

2002.

Table 82–1

Lactalbumin and other

0.4

0.7

Casein

0.9

2.7

Lactose

6.8

4.8

Fat

3.3

3.5

Water

88.5

87.0

Constituent

Human Milk (%)

Cow’s Milk (%)

Composition of Milk

proteins

Ash

0.2

0.7