Human Reproductive Cycle

Sexual reproduction in humans is regulated by regular endocrine changes, or cycles, in the

female. These cycles begin postnatally, function for variable times and can then decrease or
cease entirely. Human reproduction is regulated in females by the menstrual cycle, a regular
cyclic hormonal change which coordinate changes in the ovary and internal reproductive tract.
This cycle commences at puberty and ends at menopause. Non-primates (rats, mice, horses, pig)
reproduction is regulated in females by the estrous cycle.

The female sex hormones: estrogen and progesterone are secreted by the ovaries. The Ovary is
the primary sex organ in females.

The ovaries have two major functions:

1. Produce the female gametes or oocytes

2. Produce female hormones, estrogen and progesterone responsible for secondary sex
characteristics and menstrual cycle.

FERTILIZATION

Fertilization is a cell-cell recognition process that occurs between two distinct cells: a small
asymmetric and motile sperm cell and a large and nonmotile egg.

The stages of fertilization can be divided into four processes: 1) sperm preparation, 2) sperm-egg
recognition and binding, 3) sperm-egg fusion and 4) fusion of sperm and egg pronuclei and
activation of the zygote.

After deposition of sperms in the vagina, It takes 30 to 60 minutes to reach the ovarian end.
Movement of Sperm via the uterus is facilitated by antiperistaltic contractions of the uterine
muscles stimulated by Oxytocin and prostaglandin.

During fertilization, the sperm enter the ovum by penetrating the granulosa cells known as
corona radiate. The hyaluronidase and proteolytic enzyme in the acrosomal head of the sperm
help sperm to diffuse via the zona pellucid and inactivates other sperms from entering by
changing the membrane potential of the zona pellucida. Penetrating movement of sperm is
enabled by Catsper protein in the tail portion of the sperm.

There are four stages to fertilization:

1
1. Preparation: Capacitation and acrosome reaction. Acrosomal vesicle fusion is the membrane
fusion event of this stage.

2. Binding: Species-specific interaction of gametes.

3. Fusion: Merging of sperm and egg plasma membranes is the membrane fusion event of this
stage.

4. Activation (of the zygote): Cortical reaction (fusion of cortical vesicles with the egg plasma
membrane) and pronuclear fusion.

Note that:

Fertilization resulting in embryo development usually occurs in first 1/3 (ampula) of fallopian
tube. The majority of fertilized oocytes do not go on to form an embryo, Fertilization can also
occur outside uterine tube associated with Assisted Reproductive Technologies (IVF, GIFT,
ZIFT...).

Oocyte ovulation - release from the ovary with associated cells, into peritoneal cavity, fallopian
tube fimbria then into fallopian tube. Epithelial cilia mediated movement help the oocyte to
move along the tube. Eggs are large (~100 µm), symmetrical and nonmotile cell (does not move
on its own)

Deposited sperms in the vagina, have approximately 24-48h to locate and fertilize the oocyte.

Human eggs are arrested in metaphase of the second meiotic division and complete meiosis only
upon fertilization. Their surface is covered by microvilli. Eggs are surrounded by a zona pellucid
which is a glycoprotein coat composed of three glycoproteins ( ZPGP I-III). The zona pellucida
is not an osmotic barrier (in fact, even virus are capable of penetrating it), however it is a barrier
to the sperm. The zona pellucida is a specie specific barrier to fertilization.

Fertilization is evidenced by the formation of pronuclei.

IMPLANTATION

Fertilization occurs in the fallopian tube within 24 to 48 hours after ovulation.The initial stages
of development, from fertilized ovum (zygote) to a mass of 12 to 16 cells (morula), occur as the
embryo, encased in a non adhesive protective coating known as the zona pellucida, passes
through the fallopian tube. The morula enters the uterine cavity approximately two to three days
after fertilization. The appearance of a fluid-filled inner cavity within the mass of cells marks the
transition from morula to blastocyst and is accompanied by cellular differentiation: the surface
cells become the trophoblast (and give rise to extra embryonic structures, including the placenta),
and the inner cell mass gives rise to the embryo. Within 72hours after entering the uterine cavity,
the embryo hatches from the zona, thereby exposing its outer covering of syncytial
(multinucleate) trophoblasts.
2
Implantation is the process of attachment and invasion of the uterine endometrium by the
blastocyst (conceptus).

Implantation occurs approximately six or seven days after fertilization.

Stages of Implantation

The initial adhesion of the blastocyst to the uterine wall, called apposition, is unstable. Microvilli
on the apical surface of syncytiotrophoblasts interdigitate with micro protrusions from the apical
surface of the uterine epithelium, known as pinopodes. Apposition, and consequently
implantation, occurs most commonly in the upper posterior (fundal) wall of the uterus. The next
stage, stable adhesion, is characterized by increased physical interaction between the blastocyst
and the uterine epithelium. Shortly there- after, invasion begins, and syncytiotrophoblasts
penetrate the uterine epithelium. By then, the blastocyst is oriented with its embryonic pole
toward the uterine epithelium.

By the 10th day after conception, the blastocyst is completely embedded in the stromal tissue of
the uterus, the uterine epithelium has regrown to cover the site of implantation, and mononuclear
cytotrophoblasts stream out of the trophoblast layer. Eventually, cytotrophoblasts invade the
entire endometrium and the inner third of the myometrium (a process termed in terstitial
invasion), as well as the uterine vasculature (endo vascular invasion). The latter process, which
establishes the uteroplacental circulation, places trophoblasts in direct contact with maternal
blood.

Before implantation, the blastocyst obtains its nutrition from the uterine endometrial secretions,
called “uterine milk.”
Implantation results from the action of trophoblast cells that develop over the surface of the
blastocyst. These cells secrete proteolytic enzymes that digest and 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 blastocyst thereby adding more sustenance for growth. Once
implantation has taken place, the trophoblast cells and other adjacent cells (from the blastocyst
and the uterine endometrium) proliferate rapidly to form the placenta and the various
membranes of pregnancy.

EARLY NUTRITION OF THE EMBRYO

Progesterone secreted by the ovarian corpus luteum during the latter half of each monthly sexual
cycle has an effect on the uterine endometrium, it converts the endometrial stromal cells into
large swollen cells containing extra quantities of glycogen, proteins, lipids, and even some

3
minerals necessary for development of the conceptus. When the conceptus implants in the
endometrium, the continued secretion of progesterone causes the endometrial cells to swell
further and to store even more nutrients. These cells are now called decidual cells, and the total
mass of cells is called the decidua.
As the trophoblast cells invade the decidua, digesting and imbibing it, the stored nutrients in the
decidua are used by the embryo for growth and development.

THE PLACENTA

While the trophoblastic cords from the blastocyst are attaching to the uterus, blood capillaries
grow into the cords from the vascular system of the newly forming embryo. About 21 days after
fertilization, blood also begins to be pumped by the heart of the human embryo. Simultaneously,
blood sinuses supplied with blood from the mother develop around the outsides of the tropho-
blastic cords. The trophoblast cells send out more and more projections, which become placental
villi into which fetal capillaries grow. Thus, the villi, carrying fetal blood, are surrounded by
sinuses that contain maternal blood.
The fetus’s blood flows through two umbilical arteries, then into the capillaries of the villi, and
finally back through a single umbilical vein into the fetus. At the same time, the mother’s blood
flows from her uterine arteries into large maternal sinuses that surround the villi and then back
into the uterine veins of the mother.
The total surface area of all the villi of the mature placenta is only a few square meters—many
times less than the area of the pulmonary membrane in the lungs. Nutrients and other substances
pass through this placental membrane mainly by diffusion in much the same manner that
diffusion occurs through the alveolar membranes of the lungs and the capillary membranes
elsewhere in the body.

PLACENTAL PERMEABILITY AND MEMBRANE DIFFUSION CONDUCTANCE

The major function of the placenta is to provide for diffusion of digested food molecule and
oxygen from the mother’s blood into the fetus’s blood and diffusion of excretory products from
the fetus back into the mother.
In the early months of pregnancy, the placental membrane is still thick because it is not fully
developed. Therefore, its permeability is low. Further, the surface area is small because the

4
placenta has not grown significantly. Therefore, the total diffusion conductance is minuscule at
first. Conversely, in later pregnancy, the permeability increases because of thinning of the
membrane diffusion layers and because the surface area expands many times over, thus giving
the tremendous increase in placental diffusion.
Diffusion of Oxygen, CO2 and Other nutrients through the Placental Membrane.

Dissolved oxygen in the blood of the large maternal sinuses passes into the fetal blood by simple
diffusion, driven by an oxygen pressure gradient from the mother’s blood to the fetus’s blood.
Near the end of pregnancy, the mean partial pressure of oxygen (PO2) of the mother’s blood in
the placental sinuses is about 50 mm Hg, and the mean PO2 in the fetal blood after it becomes
oxygenated in the placenta is about 30 mm Hg. Therefore, the mean pressure gradient for dif-
fusion of oxygen through the placental membrane is about 20 mm Hg.

One might wonder how it is possible for a fetus to obtain sufficient oxygen when the fetal blood
leaving the placenta has a PO2 of only 30 mm Hg. There are three reasons why even this low
PO2 is capable of allowing the fetal blood to transport almost as much oxygen to the fetal tissues
as is transported by the mother’s blood to her tissues.
First, the hemoglobin of the fetus is mainly fetal hemoglobin, which is a type of hemoglobin
synthesized in the fetus before birth. This means that at the low PO2 levels in fetal blood, the
fetal hemoglobin can carry 20 to 50 percent more oxygen than can maternal hemoglobin.
Second, the hemoglobin concentration of fetal blood is about 50 percent greater than that of the
mother, which is an even more important factor in enhancing the amount of oxygen transported
to the fetal tissues.
Third, the Bohr effect, which is explained in relation to the exchange of carbon dioxide and
oxygen in the lung, provides another mechanism to enhance the transport of oxygen by fetal
blood. That is, hemoglobin can carry more oxygen at a low PCO2 than it can at a high PCO2.
The fetal blood entering the placenta carries large amounts of carbon dioxide, but much of this
carbon dioxide diffuses from the fetal blood into the maternal blood. Loss of the carbon dioxide
makes the fetal blood more alkaline, whereas the increased carbon dioxide in the maternal blood
makes it more acidic.
These changes cause the capacity of fetal blood to combine with oxygen to increase and that
of maternal blood to decrease, which forces still more oxygen from the maternal blood while

5
enhancing oxygen uptake by the fetal blood. Thus, the Bohr shift operates in one direction in the
maternal blood and in the other direction in the fetal blood. These two effects make the Bohr
shift twice as important here as it is for oxygen exchange in the lungs; therefore, it is called the
double Bohr effect.
By these three means, the fetus is capable of receiving more than adequate oxygen through the
placental membrane, despite the fact that the fetal blood leaving the placenta has a PO2 of only
30 mm Hg.
The total 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 difference across the membrane,
which compares favorably with that of the lungs of the newborn baby.

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
tissues, and the only means for excreting the carbon dioxide from the fetus is through the
placenta into the mother’s blood. The partial pressure of carbon dioxide (PCO2) of the fetal
blood is 2 to 3 mm Hg higher than that of the maternal blood. This small pressure gradient for
carbon dioxide across the membrane is more than sufficient to allow adequate diffusion of
carbon dioxide because the extreme solubility of carbon dioxide in the placental membrane
allows carbon dioxide to diffuse about 20 times as rapidly as oxygen.

Diffusion of Nutrients through the Placental Membrane. Other metabolic substrates needed
by the fetus diffuse into the fetal blood in the same manner as oxygen does. For instance, in the
late stages of pregnancy, the fetus often uses as much glucose as is used by the entire body of the
mother. To provide this much glucose, the trophoblast cells lining the placental villi provide for
facilitated diffusion of glucose through the placental membrane—that is, the glucose is
transported by carrier molecules in the trophoblast cells of the membrane. Even so, the glucose
level in fetal blood is 20 to 30 percent lower than that in maternal blood.
Because of the high solubility of fatty acids in cell membranes, these fatty acids also diffuse
from the maternal blood into the fetal blood, but more slowly than glucose, so glucose is used
more easily by the fetus for nutrition. Also, such substances as ketone bodies and potassium,
sodium, and chloride ions diffuse with relative ease from the maternal blood into the fetal blood.

6
Excretion of Waste Products Through the Placental Membrane. In the same manner that
carbon dioxide diffuses from the fetal blood into the maternal blood, other excretory products
formed in the fetus also diffuse through the placental membrane into the maternal blood and are
then excreted along with the excretory products of the mother. These products include especially
the onprotein nitrogens such as urea, uric acid, and creatinine. The level of urea in fetal blood
is only slightly greater than that in maternal blood because urea diffuses through the placental
membrane with great ease. However, creatinine, which does not diffuse as easily, has a fetal
blood concentration considerably higher than that in the mother’s blood. Therefore, excretion
from the fetus depends mainly, if not entirely, on the diffusion gradients across the placental
membrane and its permeability. Because there are higher concentrations of the excretory
products in the fetal blood than in the maternal blood, there is continual diffusion of these
substances from the fetal blood to the maternal blood.

HORMONAL FACTORS IN PREGNANCY

In pregnancy, the placenta forms especially large quantities of human chorionic gonadotropin,
estrogens, progesterone, and human chorionic somatomammotropin. These hormones are all
essential for a normal pregnancy.

HUMAN CHORIONIC GONADOTROPIN CAUSES PERSISTENCE OF THE

CORPUS LUTEUM AND PREVENTS MENSTRUATION

Menstruation normally occurs in a nonpregnant woman about 14 days after ovulation, at which
time most of the endometrium of the uterus sloughs away from the uterine wall and is expelled to
the exterior. If this should happen after an ovum has implanted, the pregnancy would terminate.
However, this sloughing is prevented by the secretion of human chorionic gonadotropin by the
newly developing embryonic tissues.
Coincidental with the development of the trophoblast cells from the early fertilized ovum, the
hormone human chorionic gonadotropin is secreted by the syncytial trophoblast cells into the
fluids of the mother. The secretion of this hormone can first be measured in the blood 8 to 9 days
after ovulation, shortly after the blastocyst implants in the endometrium. Then the rate of
secretion rises rapidly to reach a maximum at about 10 to 12 weeks of pregnancy and decreases

7
back to a lower value by 16 to 20 weeks. It continues at this level for the remainder of the
pregnancy.

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 hormone secreted by the pituitary gland. By far, the most important
function of human chorionic gonadotropin is to prevent involution of the corpus luteum at the
end of the monthly female sexual cycle. Instead, it causes the corpus luteum to secrete even
larger quantities of its sex hormones— progesterone and estrogens—for the next few months.
These sex hormones prevent menstruation and cause the endometrium to continue to grow and
store large amounts of nutrients rather than being shed in the menstruum. As a result, the
decidua-like cells that develop in the endometrium during the normal female sexual cycle
become actual decidual cells.
If the corpus luteum is removed before approximately the seventh week of pregnancy,
spontaneous abortion almost always occurs, sometimes even up to the 12th week. After that
time, the placenta secretes sufficient quantities of progesterone and estrogens to maintain
pregnancy for the remainder of the gestation period. The corpus luteum involutes slowly after the
13th to 17th week of gestation.

Human Chorionic Gonadotropin Stimulates the Male Fetal Testes to Produce Testosterone.
Human chorionic gonadotropin also exerts an interstitial cell– stimulating effect on the testes of
the male fetus, resulting in the production of testosterone in male fetuses until the time of birth.
This small secretion of testosterone during gestation is what causes the fetus to grow male sex
organs instead of female organs. Near the end of pregnancy, the testosterone secreted by the fetal
testes also causes the testes to descend into the scrotum.

SECRETION OF ESTROGENS BY THE PLACENTA

The placenta, like the corpus luteum, secretes both estrogens and progesterone. Histochemical
and physiological studies show that these two hormones, like most other placental hormones, are
secreted by the syncytial trophoblast cells of the placenta.
Toward the end of pregnancy, the daily production of placental estrogens increases to about 30
times the mother’s normal level of production. However, the secretion of estrogens by the

8
placenta is quite different from secretion by the ovaries. Most important, the estrogens secreted
by the placenta are not synthesized de novo from basic substrates in the placenta. Instead, they
are formed almost entirely from androgenic steroid compounds, dehydroepiandrosterone and 16-
hydroxydehydroepiandrosterone, which are formed both in the mother’s adrenal glands and in
the adrenal glands of the fetus. These weak androgens are transported by the blood to the
placenta and converted by the trophoblast cells into estradiol, estrone, and estriol. (The cortices
of the fetal adrenal glands are extremely large, and about 80 percent consists of a so-called fetal
zone, the primary function of which seems to be to secrete dehydroepiandrosterone during
pregnancy).

Function of Estrogen in Pregnancy. Estrogens exert mainly a proliferative function on most

reproductive and associated organs of the mother. During pregnancy, the extreme quantities of
estrogens cause (1) enlargement of the mother’s uterus, (2) enlargement of the mother’s breasts
and growth of the breast ductal structure, and (3) enlargement of the mother’s female external
genitalia.

The estrogens also relax the pelvic ligaments of the mother, so the sacroiliac joints become
relatively limber and the symphysis pubis becomes elastic. These changes allow easier
passage of the fetus through the birth canal.

SECRETION OF PROGESTERONE BY THE PLACENTA

Progesterone is also essential for a successful pregnancy; in fact, it is just as important as

estrogen. In addition to being secreted in moderate quantities by the corpus luteum at the
beginning of pregnancy, progesterone is secreted later in tremendous quantities by the placenta.
The following special effects of progesterone are essential for the normal progression of
pregnancy:
1. Progesterone causes decidual cells to develop in the uterine endometrium. These cells play
an important role in the nutrition of the early embryo.
2. Progesterone decreases the contractility of the pregnant uterus, thus preventing uterine
contractions from causing spontaneous abortion.
3. Progesterone contributes to the development of the conceptus even before implantation
because it specifically increases the secretions of the mother’s fallopian tubes and uterus to

9
 provide appropriate nutritive matter for the developing morula (the spherical mass of 16 to
32 blastomeres formed before the blastula) and blastocyst. There is also reason to believe
that progesterone affects cell cleavage in the early developing embryo.
4. The progesterone secreted during pregnancy helps estrogen prepare the mother’s breasts for
lactation, which is discussed later in this chapter.

HUMAN CHORIONIC SOMATOMAMMOTROPIN

Human chorionic somatomammotropin, a protein hormone with a molecular weight of about

22,000, begins to be secreted by the placenta at about the fifth week of pregnancy. Secretion of
this hormone increases progressively throughout the remainder of pregnancy in direct proportion
to the weight of the placenta. Although the functions of chorionic somatomammotropin are
uncertain, it is secreted in quantities several times greater than that of all the other pregnancy
hormones combined. It has several possible important effects.
First, when administered to several types of animals, human chorionic somatomammotropin
causes at least partial development of the animal’s breasts and in some instances causes lactation.
Because this was the first function of the hormone that was discovered, it was first named human
placental lactogen and was believed to have functions similar to those of prolactin. However,
attempts to use it to promote lactation in humans have not been successful.
Second, this hormone has weak actions similar to those of growth hormone, causing the
formation of protein tissues in the same way that growth hormone does. It also has a chemical
structure similar to that of growth hormone, but 100 times as much human chorionic
somatomammotropin as growth hormone is required to promote growth.
Third, human chorionic somatomammotropin causes decreased insulin sensitivity and decreased
utilization of glucose in the mother, thereby making larger quantities of glucose available to the
fetus. Because glucose is the major substrate used by the fetus to energize its growth, the
possible importance of such a hormonal effect is obvious. Further, the hormone promotes the
release of free fatty acids from the fat stores of the mother, thus providing this alternative source
of energy for the mother’s metabolism during pregnancy. Therefore, it appears that human
chorionic somatomammotropin is a general metabolic hormone that has specific nutritional
implications for both the mother and the fetus.

10
Other Hormonal Factors in Pregnancy

Almost all the nonsexual endocrine glands of the mother also react markedly to pregnancy.
This reaction results mainly from the increased metabolic load on the mother but also, to some
extent, from the effects of placental hormones on the pituitary and other glands. The following
effects are some of the most notable.
Pituitary Secretion. The anterior pituitary gland of the mother enlarges at least 50 percent
during pregnancy and increases its production of corticotropin, thyrotropin, and prolactin.
Conversely, pituitary secretion 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.
Increased Corticosteroid Secretion. The rate of adrenocortical secretion of the
glucocorticoids is moderately increased throughout pregnancy. It is possible that these
glucocorticoids help mobilize amino acids from the mother’s tissues so these amino acids can
be used for the synthesis of tissues in the fetus.
Pregnant women usually have about a twofold increase in aldosterone secretion, reaching a
peak at the end of gestation. This increase, along with the actions of estrogens, causes a
tendency for even a normal pregnant woman to reabsorb excess sodium from her renal tubules
and, therefore, to retain fluid, which occasionally leads to pregnancy-induced hypertension.
Increased Thyroid Gland Secretion. The mother’s thyroid gland ordinarily enlarges up to 50
percent during pregnancy and increases its production of thyroxine a corresponding amount.
The increased thyroxine production is caused at least partly by a thyrotropic effect of human
chorionic gonadotropin secreted by the placenta and by small quantities of a specific thyroid-
stimulating hormone, human chorionic thyrotropin, also secreted by the placenta.
Increased Parathyroid Gland Secretion. The mother’s parathyroid glands usually enlarge
during pregnancy; this enlargement especially occurs if the mother’s diet is deficient in calcium.
Enlargement of these glands causes calcium absorption from the mother’s bones, thereby
maintaining normal calcium ion concentration in the mother’s extracellular fluid even while the
fetus removes calcium to ossify its own bones. This secretion of parathyroid hormone is even
more intensified during lactation after the baby’s birth because the growing baby requires many
times more calcium than does the fetus.

11
Secretion of “Relaxin” by the Ovaries and Placenta. Relaxin is a 48–amino acid
polypeptide with a molecular weight of about 9000. This hormone, when injected, causes
relaxation of the ligaments of the symphysis pubis in the estrous rat and guinea pig. This effect
is weak or possibly even absent in pregnant women. Instead, this role is probably played
mainly by the estrogens, which also cause relaxation of the pelvic ligaments. It has also been
claimed that relaxin softens the cervix of the pregnant woman at the time of delivery. Relaxin
is also thought to serve as a vasodilator, contributing to increased blood flow in various tissues,
including the kidneys, and increasing venous return and cardiac output in pregnancy.

Response of the Mother’s Body to Pregnancy

Most apparent among the many reactions of the mother to the fetus and to the higher levels of
hormones of pregnancy is the increased size of the various sexual organs. For instance, the
uterus increases from about 50 grams to 1100 grams, and the breasts approximately double
in size. At the same time, the vagina enlarges and the introitus opens more widely. Also, the
various hormones can cause marked changes in a pregnant woman’s appearance, sometimes
resulting in the development of edema, acne, and masculine or acromegalic features.

Weight Gain in the Pregnant Woman

The average weight gain during pregnancy is about 25 to 35 pounds, with most of this gain
occurring during the last two trimesters. Of this added weight, about 8 pounds is fetus and 4
pounds is amniotic fluid, placenta, and fetal membranes. The uterus increases about 3 pounds
and the breasts another 2 pounds, still leaving an average weight increase of 8 to 18 pounds.
About 5 pounds of this added weight is extra fluid in the blood and extracellular fluid, and the
remaining 3 to 13 pounds is generally fat accumulation. The extra fluid is excreted in the urine
during the first few days after birth—that is, after loss of the fluid-retaining hormones from the
placenta.
During pregnancy, a woman often has a greatly increased desire for food, partly as a result of
removal of food substrates from the mother’s blood by the fetus and partly because of
hormonal factors. Without appropriate prenatal control of diet, the mother’s weight gain can be
as great as 75 pounds instead of the usual 25 to 35 pounds.

Metabolism during Pregnancy

12
As a consequence of the increased secretion of many hormones during pregnancy, including
thyroxine, adrenocortical hormones, and the sex hormones, the basal metabolic rate of the
pregnant woman increases about 15 percent during the latter half of pregnancy. As a result, she
frequently has sensations of becoming overheated. Also, owing to the extra load she is
carrying, greater amounts of energy than normal must be expended for muscle activity.

Nutrition During Pregnancy

By far the greatest growth of the fetus occurs during the last trimester of pregnancy; its
weight almost doubles during the last 2 months of pregnancy. Ordinarily, the mother does not
absorb sufficient protein, calcium, phosphates, and iron from her diet during the last months
of pregnancy to supply these extra needs of the fetus. However, in anticipation of these extra
needs, the mother’s body has already been storing these substances—some in the placenta,
but most in the normal storage depots of the mother.
If appropriate nutritional elements are not present in a pregnant woman’s diet, several
maternal deficiencies can occur, especially in calcium, phosphates, iron, and the vitamins.
For example, the fetus needs about 375 milligrams of iron to form its blood, and the mother
needs an additional 600 milligrams to form her own extra blood. The normal store of
nonhemoglobin iron in the mother at the outset of pregnancy is often only 100 milligrams
and almost never more than 700 milligrams. Therefore, without sufficient iron in her food,
a pregnant woman usually develops hypochromic anemia. Also, it is especially important
that she receive vitamin D, because although the total quantity of calcium used by the fetus is
small, calcium is normally poorly absorbed by the mother’s gastrointestinal tract without
vitamin D. Finally, shortly before birth of the baby, vitamin K is often added to the mother’s
diet so the baby will have sufficient prothrombin to prevent hemorrhage, particularly brain
hemorrhage, caused by the birth process.

Changes in the Maternal Circulatory System During Pregnancy

Blood Flow Through the Placenta and Maternal Cardiac Output Increase During
Pregnancy.
About 625 milliliters of blood flows through the maternal circulation of the placenta each
minute during the last month of pregnancy. This flow, plus the general increase in the
mother’s metabolism, increases the mother’s cardiac output to 30 to 40 percent above normal

13
by the 27th week of pregnancy; then, for unexplained reasons, the cardiac output falls to only
a little above normal during the last 8 weeks of pregnancy, despite the high uterine blood
flow, indicating that blood flow in some other tissue(s) may be reduced.
Maternal Blood Volume Increases During Pregnancy. The maternal blood volume shortly
before term is about 30 percent above normal. This increase occurs mainly during the latter half
of pregnancy. The cause of the increased volume is likely due, at least in part, to aldosterone and
estrogens, which are greatly increased in pregnancy, and to increased fluid retention by the
kidneys. In addition, the bone marrow becomes increasingly active and produces extra red blood
cells to go with the excess fluid volume. Therefore, at the time of the birth of the baby, the
mother has about 1 to 2 liters of extra blood in her circulatory system. Only about one fourth of
this amount is normally lost through bleeding during delivery of the baby, thereby allowing a
considerable safety factor for the mother.
Maternal Respiration Increases During Pregnancy. Because of the increased basal metabolic
rate of a pregnant woman and because of her greater size, the total amount of oxygen used by the
mother shortly before the birth of the baby is about 20 percent above normal, and a com-
mensurate amount of carbon dioxide is formed. These effects cause the mother’s minute
ventilation to increase. It is also believed that the high levels of progesterone during pregnancy
increase the minute ventilation even more, because progesterone increases the sensitivity of the
respiratory center to carbon dioxide. The net result is an increase in minute ventilation of about
50 percent and a decrease in arterial PCO2 to several millimeters of mercury below that in a
nonpregnant woman. Simultaneously, the growing uterus presses upward against the abdominal
contents, which press upward against the diaphragm, so the total excursion of the diaphragm is
decreased. Consequently, the respiratory rate is increased to maintain the extra ventilation.
Maternal Kidney Function During Pregnancy
The rate of urine formation by a pregnant woman is usually slightly increased because of
increased fluid intake and increased load of excretory products. In addition, several special
alterations of kidney function occur.
First, the renal tubules’ reabsorptive capacity for sodium, chloride, and water is increased as
much as 50 percent as a consequence of increased production of salt and water-retaining
hormones, especially steroid hormones by the placenta and adrenal cortex.

14
Second, the renal blood flow and glomerular filtration rate increase up to 50 percent during
normal pregnancy as a result of renal vasodilation. Although the mechanisms that cause renal
vasodilation in pregnancy are still unclear, some studies suggest that increased levels of nitric
oxide or the ovarian hormone relaxin may contribute to these changes. The increased
glomerular filtration rate likely occurs, at least in part, as a compensation for increased tubular
reabsorption of salt and water. Thus, the normal pregnant woman ordinarily accumulates only
about 5 pounds of extra water and salt.
Amniotic Fluid and Its Formation Normally, the volume of amniotic fluid (the fluid inside
the uterus in which the fetus floats) is between 500 milliliters and 1 liter, but it can be only a
few milliliters or as much as several liters. Isotope studies of the rate of formation of amniotic
fluid show that, on average, the water in amniotic fluid is replaced once every 3 hours and
the electrolytes sodium and potassium are replaced an average of once every 15 hours. A
large portion of the fluid is derived from renal excretion by the fetus. Likewise, a certain
amount of absorption occurs by way of the gastrointestinal tract and lungs of the fetus.
However, even after in utero death of a fetus, some turnover of the amniotic fluid still occurs,
which indicates that some of the fluid is formed and absorbed directly through the amniotic
membranes.

Preeclampsia and Eclampsia

About 5 percent of all pregnant women experience pregnancy-induced hypertension, that is, a
rapid rise in arterial blood pressure to hypertensive levels during the last few months of
pregnancy that is also associated with leakage of large amounts of protein into the urine.
This condition is called preeclampsia or toxemia of pregnancy. It is often characterized by
excess salt and water retention by the mother’s kidneys and by weight gain and the devel-
opment of edema and hypertension in the mother. In addition, function of the vascular
endothelium is impaired and arterial spasm occurs in many parts of the mother’s body, most
significantly in the kidneys, brain, and liver. Both the renal blood flow and the glomerular
filtration rate are decreased, which is exactly opposite to the changes that occur in the normal
pregnant woman. The renal effects also include thickened glomerular tufts that contain a
protein deposit in the basement membranes.

15
Various attempts have been made to prove that preeclampsia is caused by excessive secretion
of placental or adrenal hormones, but proof of a hormonal basis is still lacking. Another theory
is that preeclampsia results from some type of autoimmunity or allergy in the mother caused by
the presence of the fetus. In support of this theory, the acute symptoms usually disappear
within a few days after birth of the baby.
Evidence also indicates that preeclampsia is initiated by insufficient blood supply to the
placenta, resulting in the placenta’s release of substances that cause widespread dysfunction
of the maternal vascular endothelium. During normal placental development, the trophoblasts
invade the arterioles of the uterine endometrium and completely remodel the maternal
arterioles into large blood vessels with low resistance to blood flow. In women with pre-
eclampsia, the maternal arterioles fail to undergo these adaptive changes, for reasons that are
still unclear, and blood supply to the placenta is insufficient. This insufficient blood supply,
in turn, causes the placenta to release various substances that enter the mother’s circulation
and cause impaired vascular endothelial function, decreased blood flow to the kidneys,
excess salt and water retention, and increased blood pressure.
Eclampsia is an extreme degree of preeclampsia characterized by vascular spasm throughout the
body; clonic seizures in the mother, sometimes followed by coma; greatly decreased kidney
output; malfunction of the liver; often extreme hypertension; and a generalized toxic condition of
the body. It usually occurs shortly before the birth of the baby. Without treatment, a high
percentage of mothers with eclampsia die. However, with optimal and immediate use of rapidly
acting vasodilating drugs to reduce the arterial pressure to normal, followed by immediate
termination of pregnancy—by cesarean section if necessary—the mortality even in mothers with
eclampsia has been reduced to 1 percent or less.

PARTURITION

INCREASED UTERINE EXCITABILITY NEAR TERM

Parturition means birth of the baby. Toward the end of pregnancy, the uterus becomes
progressively more excitable, until finally it develops such strong rhythmical contractions that
the baby is expelled. The exact cause of the increased activity of the uterus is not known, but at
least two major categories of effects lead up to the intense contractions responsible for

16
parturition: (1) progressive hormonal changes that cause increased excitability of the uterine
musculature and (2) progressive mechanical changes.

Hormonal Factors That Increase Uterine Contractility

Increased Ratio of Estrogens to Progesterone. Progesterone inhibits uterine contractility

during pregnancy, thereby helping to prevent expulsion of the fetus. Conversely, estrogens have
a definite tendency to increase the degree of uterine contractility, partly because estrogens
increase the number of gap junctions between the adjacent uterine smooth muscle cells, but also
because of other poorly understood effects. Both progesterone and estrogen are secreted in
progressively greater quantities throughout most of pregnancy, but from the seventh month
onward, estrogen secretion continues to increase while progesterone secretion remains constant
or perhaps even decreases slightly. Therefore, it has been postulated that the estrogen-to-
progesterone ratio increases sufficiently toward the end of pregnancy to be at least partly
responsible for the increased contractility of the uterus.

Oxytocin Causes Contraction of the Uterus. Oxytocin, a hormone secreted by the

neurohypophysis, specifically causes uterine contraction. There are four reasons to believe that
oxytocin might be important in increasing the contractility of the uterus near term:
1. The uterine muscle increases its oxytocin receptors and therefore increases its
responsiveness to a given dose of oxytocin during the latter few months of pregnancy.
2. The rate of oxytocin secretion by the neurohypophysis is considerably increased at the
time of labor.
3. Although hypophysectomized animals can still deliver their young at term, labor is
prolonged.
4. Experiments in animals indicate that irritation or stretching of the uterine cervix, as
occurs during labor, can cause a neurogenic reflex 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. The fetus’s pituitary gland secretes increasing
quantities of oxytocin, which might play a role in exciting the uterus. Also, the fetus’s adrenal
glands secrete large quantities of cortisol, another possible uterine stimulant. In addition, the fetal

17
membranes release prostaglandins in high concentration at the time of labor. These
prostaglandins, too, can increase the intensity of uterine contractions.

Mechanical Factors That Increase Uterine Contractility

Stretch of the Uterine Musculature. Simply stretching smooth muscle organs usually increases
their contractility. Further, intermittent stretch, which occurs repeatedly in the uterus because of
fetal movements, can also elicit smooth muscle contraction. Note especially that twins are born,
on average, 19 days earlier than a single child, which emphasizes the importance of mechanical
stretch in eliciting uterine contractions.

ONSET OF LABOR—A POSITIVE FEEDBACK MECHANISM FOR ITS

INITIATION

During most of the months of pregnancy, the uterus undergoes periodic episodes of weak and
slow rhythmical contractions called Braxton Hicks contractions. These contractions become
progressively stronger toward the end of pregnancy; then they change suddenly, within hours, to
become exceptionally strong contractions that start stretching the cervix and later force the baby
through the birth canal, thereby causing parturition. This process is called labor, and the strong
contractions that result in final parturition are called labor contractions.
Proposed theory to explain the onset of labor:
The positive feedback theory suggests that stretching of the cervix by the fetus’s head finally
becomes great enough to elicit a strong reflex increase in contractility of the uterine body. This
pushes the baby forward, which stretches the cervix more and initiates more positive feedback to
the uterine body. Thus, the process repeats until the baby is expelled.
First, labor contractions obey all the principles of positive feedback. That is, once the strength of
uterine contraction becomes greater than a critical value, each contraction leads to subsequent
contractions that become stronger and stronger until maximum effect is achieved.
Second, two known types of positive feedback increase uterine contractions during labor: (1)
Stretching of the cervix causes the entire body of the uterus to contract, and this contraction
stretches the cervix even more because of the downward thrust of the baby’s head, and (2)
cervical stretching also causes the pituitary gland to secrete oxytocin, which is another means for
increasing uterine contractility.

18
ABDOMINAL MUSCLE CONTRACTIONS DURING LABOR

Once uterine contractions become strong during labor, pain signals originate both from the uterus
and from the birth canal. These signals, in addition to causing suffering, elicit neurogenic
reflexes in the spinal cord to the abdominal muscles, causing intense contractions of these
muscles. The abdominal contractions add greatly to the force that causes expulsion of the baby.

Mechanics of Parturition

The uterine contractions during labor begin mainly at the top of the uterine fundus and spread
downward over the body of the uterus. Also, the intensity of contraction is great in the top and
body of the uterus but weak in the lower segment of the uterus adjacent to the cervix. Therefore,
each uterine contraction tends to force the baby downward toward the cervix.

In the early part of labor, the contractions might occur only once every 30 minutes. As labor
progresses, the contractions finally appear as often as once every 1 to 3 minutes and the
intensity of contraction increases greatly, with only a short period of relaxation between
contractions. The combined contractions of the uterine 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 intermittently, because strong contractions
impede or sometimes even stop blood flow through the placenta and would cause death of the
fetus if the contractions were continuous. Indeed, overuse of various uterine stimulants, such as
oxytocin, can cause uterine spasm rather than rhythmical contractions and can lead to death of
the fetus.
In more than 95 percent of births, the head is the first part of the baby to be expelled, and in
most of the remaining instances, the buttocks are presented first. Entering the birth canal with
the buttocks or feet first is called a breech presentation.
The head acts as a wedge to open the structures of the birth canal as the fetus is forced
downward. The first major obstruction to expulsion of the fetus is the uterine cervix. Toward
the end of pregnancy, the cervix becomes soft, which allows it to stretch when labor
contractions begin in the uterus. The so-called first stage of labor is a period of progressive
cervical dilation, lasting until the cervical opening is as large as the head of the fetus. This

19
stage usually lasts for 8 to 24 hours in the first pregnancy but often only a few minutes after
many pregnancies.
Once the cervix has dilated fully, the fetal membranes usually rupture and the amniotic fluid is
lost suddenly through the vagina. Then the head of the fetus moves rapidly into the birth canal,
and with additional force from above, it continues to wedge its way through the canal until
delivery occurs. This is called the second stage of labor, and it may last from as little as 1
minute after many pregnancies to 30 minutes or more in the first pregnancy.

Separation and Delivery of the Placenta

For 10 to 45 minutes after birth of the baby, the uterus continues to contract to a smaller and
smaller size, which causes a shearing effect between the walls of the uterus and the placenta,
thus separating the placenta from its implantation site. Separation of the placenta opens the
placental sinuses and causes bleeding. The amount of bleeding is limited to an average of 350
milliliters by the following mechanism: The smooth muscle fibers of the uterine musculature
are arranged in figures of eight around the blood vessels as the vessels pass through the uterine
wall. Therefore, contraction of the uterus after delivery of the baby constricts the vessels that
had previously supplied blood to the placenta. In addition, it is believed that vasoconstrictor
prostaglandins formed at the placental separation site cause additional blood vessel spasm.

Labor Pains

With each uterine contraction, the mother experiences considerable pain. The cramping pain
in early labor is probably caused mainly by hypoxia of the uterine muscle resulting from
compression of the blood vessels in the uterus. This pain is not felt when the visceral sensory
hypogastric nerves, which carry the visceral sensory fibers leading from the uterus, have been
sectioned.
During the second stage of labor, when the fetus is being expelled through the birth canal,
much more severe pain is caused by cervical stretching, perineal stretching, and stretching or
tearing of structures in the vaginal canal itself. This pain is conducted to the mother’s spinal
cord and brain by somatic nerves instead of by the visceral sensory nerves.

Involution of the Uterus after Parturition

During the first 4 to 5 weeks after parturition, the uterus involutes. Its weight becomes less than
half its immediate postpartum weight within 1 week, and in 4 weeks, if the mother lactates, the

20
uterus may become as small as it was before pregnancy. This effect of lactation results from the
suppression of pituitary gonadotropin and ovarian hormone secretion during the first few months
of lactation. During early involution of the uterus, the placental site on the endometrial surface
autolyzes, causing a vaginal discharge known as lochia, which is first bloody and then serous in
nature and continues for a total of about 10 days. After this time, the endometrial surface
becomes re-epithelialized and ready for normal, nongravid sex life again.

LACTATION

DEVELOPMENT OF THE BREASTS

The breasts begin to develop at puberty. This development is stimulated by the estrogens of the
monthly female sexual cycle; estrogens stimulate growth of the breasts’ mammary glands plus
the deposition of fat to give the breasts mass. In addition, far greater growth occurs during the
high-estrogen state of pregnancy, and only then does the glandular tissue become completely
developed for the production of milk.

Estrogens Stimulate Growth of the Ductal System of the Breasts. All through pregnancy, the
large quantities of estrogens secreted by the placenta cause the ductal system of the breasts to
grow and branch. Simultaneously, the stroma of the breasts increases in quantity, and large
quantities of fat are laid down in the stroma.
Also important for growth of the ductal system are at least four other hormones: growth
hormone, prolactin, the adrenal glucocorticoids, and insulin. Each of these hormones is known
to play at least some role in protein metabolism, which presumably explains their function in the
development of the breasts.
Progesterone Is Required for Full Development of the Lobule-Alveolar System. Final
development of the breasts into milk-secreting organs also requires progesterone. Once the
ductal system has developed, progesterone—acting synergistically with estrogen, as well as with
the other hormones just mentioned—causes additional growth of the breast lobules, with budding
of alveoli and development of secretory characteristics in the cells of the alveoli. These changes
are analogous to the secretory effects of progesterone on the endometrium of the uterus during
the latter half of the female menstrual cycle.

PROLACTIN PROMOTES LACTATION

21
Although estrogen and progesterone are essential for the physical development of the breasts
during pregnancy, a specific effect of both these hormones is to inhibit the actual secretion of
milk. Conversely, the hormone prolactin has exactly the opposite effect and promotes milk
secretion. Prolactin is secreted by the mother’s anterior pituitary gland, and its concentration in
her blood rises steadily from the fifth week of pregnancy until birth of the baby, at which time it
has risen to 10 to 20 times the normal nonpregnant level. This high level of prolactin at the end
of pregnancy.
The fluid secreted during the last few days before and the first few days after parturition is called
colostrum; it contains essentially the same concentrations of proteins and lactose as milk, but it
has almost no fat and its maximum rate of production is about 1/100 the subsequent rate of milk
production.
Immediately after the baby is born, the sudden loss of both estrogen and progesterone
secretion from the placenta allows the lactogenic effect of prolactin from the mother’s pituitary
gland to assume its natural milk-promoting role, and during the next 1 to 7 days, the breasts
begin to secrete copious quantities of milk instead of colostrum. This secretion of milk requires
an adequate background secretion of most of the mother’s other hormones as well, but most
important are growth hormone, cortisol, parathyroid hormone, and insulin. These hormones are
necessary to provide the amino acids, fatty acids, glucose, and calcium required for the formation
of milk.
After the birth of the baby, the basal level of prolactin secretion returns to the nonpregnant
level during the next few weeks. However, each time the mother nurses her baby, nervous
signals from the nipples to the hypothalamus cause a 10- to 20-fold surge in prolactin secretion
that lasts for about 1 hour, this prolactin acts on the mother’s breasts to keep the mammary
glands secreting milk into the alveoli for the subsequent nursing periods. If this prolactin surge is
absent or blocked as a result of hypothalamic or pituitary damage or if nursing does not continue,
the breasts lose their ability to produce milk within 1 week or so. However, milk production can
continue for several years if the child continues to suckle, although the rate of milk formation
normally decreases considerably after 7 to 9 months.

The Hypothalamus Secretes Prolactin Inhibitory Hormone. The hypothalamus plays an

essential role in controlling prolactin secretion, as it does for almost all the other anterior
pituitary hormones. However, this control is different in one aspect: The hypothalamus mainly

22
stimulates production of all the other hormones, but it mainly inhibits prolactin production.
Consequently, damage to the hypothalamus or blockage of the hypothalamic-hypophysial portal
system often increases prolactin secretion while it depresses secretion of the other anterior
pituitary hormones.
Therefore, it is believed that anterior pituitary secretion of prolactin is controlled either
entirely or almost entirely by an inhibitory factor formed in the hypothalamus and transported
through the hypothalamic-hypophysial portal system to the anterior pituitary gland. This factor is
sometimes called prolactin inhibitory hormone, but it is almost certainly the same as the cate-
cholamine dopamine, 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 for Many Months After
Delivery. In most nursing mothers, the ovarian cycle (and ovulation) does not resume until a few
weeks after cessation of nursing. The reason 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 or because of a subsequent effect of increased prolactin—inhibit secretion of
gonadotropin-releasing mother’s pituitary gland to assume its natural milk-promoting role, and
during the next 1 to 7 days, the breasts begin to secrete copious quantities of milk instead of
colostrum. This secretion of milk requires an adequate background secretion of most of the
mother’s other hormones as well, but most important are growth hormone, cortisol, parathyroid
hormone, and insulin. These hormones are necessary to provide the amino acids, fatty acids,
glucose, and calcium required for the formation of milk.

EJECTION (OR “LET-DOWN”) PROCESS IN MILK SECRETION—FUNCTION

OF OXYTOCIN

Milk is secreted continuously into the alveoli of the breasts, but it does not flow easily from the
alveoli into the ductal system and, therefore, does not continually leak from the nipples. Instead,
the milk must be ejected from the alveoli into the ducts before the baby can obtain it. This
ejection is caused by a combined neurogenic and hormonal reflex that involves the posterior
pituitary hormone oxytocin.
When the baby suckles, it receives virtually no milk for the first half minute or so. Sensory
impulses must first be transmitted through somatic nerves from the nipples to the mother’s spinal

23
cord and then to her hypothalamus, where they cause nerve signals that promote oxytocin
secretion at the same time that they cause prolactin secretion. The oxytocin is carried in the
blood to the breasts, where it causes myoepithelial cells (which surround the outer walls of the
alveoli) to contract, thereby expressing the milk from the alveoli into the ducts at a pressure of
+10 to 20 mm Hg. Then the baby’s suckling becomes effective in removing the milk. Thus,
within 30 seconds to 1 minute after a baby begins to suckle, milk begins to flow. This process is
called milk ejection or milk let-down.
Suckling on one breast causes milk flow not only in that breast but also in the opposite breast. It
is especially 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 psychogenic factors or even generalized sympathetic nervous system stimulation
throughout the mother’s body can inhibit oxytocin secretion and consequently depress milk
ejection. For this reason, many mothers must have an undisturbed period of adjustment after
childbirth if they are to be successful in nursing their babies.

MILK COMPOSITION AND THE METABOLIC DRAIN ON THE MOTHER

CAUSED BY LACTATION

The concentration of lactose in human milk is about 50 percent greater than in cow’s milk, but
the concentration of protein in cow’s milk is ordinarily two or more times greater than in human
milk. Finally, only one third as much ash, which contains calcium and other minerals, is found in
human milk compared with cow’s milk.
At the height of lactation in the human mother, 1.5 liters of milk may be formed each day (and
even more if the mother has twins). With this degree of lactation, great quantities of energy are
drained from the mother; approximately 650 to 750 kilocalories per liter (or 19 to 22 kilocalories
per ounce) are contained in breast milk, although the composition and caloric content of the milk
depends on the mother’s diet and other factors such as the fullness of the breasts.
Large amounts of metabolic substrates are also lost from the mother. For instance, about 50
grams of fat enter the milk each day, as well as about 100 grams of lactose, which must be
derived by conversion from the mother’s glucose. Also, 2 to 3 grams of calcium phosphate may
be lost each day; unless the mother is drinking large quantities of milk and has an adequate

24
intake of vitamin D, the output of calcium and phosphate by the lactating mammae will often be
much greater than the intake of these substances. To supply the needed calcium and phosphate,
the parathyroid glands enlarge greatly and the bones become progressively decalcified. The
mother’s bone decalcification is usually not a big problem during pregnancy, but it can become
more important during lactation.

Antibodies and Other Anti-infectious Agents in Milk. Not only does milk provide the
newborn baby with needed nutrients, but it also provides important protection against infection.
For instance, multiple types of antibodies and other anti-infectious agents are secreted in milk
along with the nutrients. Also, several different types of white blood cells are secreted, including
both neutrophils and macrophages, some of which are especially lethal to bacteria that could
cause deadly infections in newborn babies. Particularly important are antibodies and
macrophages that destroy Escherichia coli bacteria, which often cause lethal diarrhea in
newborns.
When cow’s milk is used to supply nutrition for the baby in place of mother’s milk, the
protective agents in it are usually of little value because they are normally destroyed within
minutes in the internal environment of the human being.

COMPOSITION OF MILK

CONSTITUENT HUMAN MILK (%) COW (%)

Water 88.5 87.0
Fat 3.3 3.5
Lactose 6.8 4.8
Casein 0.9 2.7
Lactalbumin and other 0.4 0.7
Proteins
Ash 0.2 0.7

25