Fertilization,
Pregnancy And Parturition
The unfertilized ovum can survive
for up to 24 h after ovulation, and sperm remain viable in the uterus for up to
5 days after ejaculation. The environment of the female tract triggers the capacitation
of sperm. This is a prerequisite for fertilization that involves
remodelling of the lipids and glycoproteins of the sperm plasma membrane,
coupled with increased metabolism and motility. The ovum is surrounded by the
zona pellucida, an acellular membrane bearing the glycoprotein ZP3 that
acts as a sperm receptor. Fertilization occurs in the oviduct, when a single
capacitated sperm binds to ZP3 and under-goes the acrosome reaction.
The acrosome is a body containing proteolytic enzymes that is attached to the
sperm head (Fig. 52a). When a sperm binds to ZP3, the acrosomal enzymes are
released to digest a pathway for the sperm to penetrate the ovum, within which
the contents of the sperm head, including its genetic material, are deposited.
This event leads to a chain of reactions that denies access to further sperm
penetration. The ovum first undergoes electrical depolarization and then
discharges granules that impair further sperm binding at the zona pellucida
(the cortical reaction). In this way, fertilization is normally
restricted to one sperm per ovum. Some 2–3 h after penetrating the ovum, the
sperm head forms the male pronucleus which joins with the female
pronucleus from the ovum (Fig. 52a). Fusion of the pronuclei combines the
parental genetic material from the gametes to form the zygote.
Pregnancy
The zygote is propelled by cilia
and muscular contractions of the Fal-lopian tube into the uterus, where it
implants in the endometrium. During this journey, the zygote undergoes a number
of cell divisions to form the morula, a solid ball of 16 cells that
‘hatches’ from the zona pellucida and develops into the blastocyst, in
which embryonic cells are surrounded by trophoblasts (Fig. 52a). The
trophoblasts are responsible for implantation, digesting away the uterine
endometrial wall to form a space for the embryo, opening up a pathway to the
maternal circulation (via the spiral arteries of the uterus) and forming
the fetal portion of the placenta. The tissue engineering activities of
trophoblasts are mediated by epidermal growth factor (EGF) (Chapter 46) and interleukin-1β. Implantation is
complete within 7–10 days of fertilization, at which time the embryo and early
placenta begin to secrete human chorionic gonadotrophin (hCG).
The appearance of hCG in the plasma and urine is one of the earliest signs of
successful conception, and its detection forms the basis of pregnancy testing
kits. hCG is a glycoprotein similar to LH that stimulates progesterone
secretion from the corpus luteum. Progesterone levels rise steadily throughout
pregnancy and fall sharply at term (Fig. 52b). This steroid ensures that the
smooth muscle of the uterus remains quiescent during gestation (essential for a
successful pregnancy), stimulates mammary gland development and prepares the
maternal brain for motherhood. The
placenta also secretes
chorionic somatomammotrophin, a growth
hormone-like protein that mobilizes metabolic fuels (Chapter 43) and promotes mammary gland growth, and
oestrogen (mainly oestriol) that stimulates uterine expansion to
accommodate the growing fetus. Fetal development occurs within a fluid-filled
sac, known as the amniotic membrane, which provides a protective buffer
against physical trauma. Pregnancy makes many physiological demands on the
mother. The ventilation rate, cardiac output and plasma volume increase to
supply fetal–maternal oxygen and water demands; the gastrointestinal absorption
of minerals is enhanced; and the renal glomerular filtration rate (Chapter 32)
rises to cope with fetal waste production.
Parturition
After some 40 weeks of gestation,
the fetus is ready for life outside the uterus. The signal that initiates
parturition in humans is still not fully understood, and there seems to be a
difference between primates and other mammals. In primates, the primary signal
is thought to arise from the fetoplacental unit (i.e. the fetus plus the
placenta) as an increase in dehydroepiandrosterone (DHEA) production from the
fetal adrenal cortex (Chapter 49), which may be driven by placental (rather
than hypothalamic) production of corticotrophin-releasing hormone (CRH)
(Chapters 44 and 49; Fig. 52a). DHEA is a precursor for oestrogen production by
the placenta. As the placental aromatase enzymes are not rate limiting, an
increase in DHEA, which is a precursor of oestrogen (Chapter 50), automatically
increases oestrogen production. Whatever the initiating signal might be, the
end result is an increase in the synthesis of prostaglandins E and F by fetal
and uterine tissues, with concomitant increases in prostaglandin receptors in
the uterine smooth muscle. The prostaglandins stimulate the production of uterine
receptors for oxytocin and change the pattern of activity in the uterine
myometrium from slow, gentle contractions to regular, deep contractions that
eventually move the fetus into the cervix. The cervix, which is softened by
prior release of the prostaglandins, dilates as the fetus is forced downwards.
At this time, the amniotic membrane ruptures. Stretching of the cervix
activates mechanoreceptors that stimulate a spinal sympathetic reflex which
causes myometrial contraction and secretion of oxytocin from the
posterior pituitary gland (Chapter 44; Fig. 52a). Oxytocin is a powerful
stimulant of uterine smooth muscle that causes further contraction of the
myometrium and pushes the fetus further into the cervix, resulting in further
stimulation of mechanoreceptors and leading to the release of more oxytocin,
i.e. this is a positive feedback system. The spinal reflex, aided by waves of
oxytocin, generates large, regular contractions of the uterus that eventually
expel the fetus and placenta through the vagina, completing the birth process.
Oxytocin continues to be useful, as it limits maternal bleeding by causing
vasoconstriction. In the fetus, oxytocin closes the ductus arteriosus, a
blood vessel that shunts blood away from the pulmonary circulation in utero,
but which would obviously hamper postpartum
life should it remain open.
