Female Reproduction Pregnancy
Fertilization and implantation
The ovum and sperm pronuclei fuse to
form the zygote, which now has the normal diploid chromosomal number
(Fig. 27a). The zygote divides mitotically as it travels along the uterine
tube, and at about 3 days after fertilization enters the uterus, when it is now
a morula. The cells of the morula continue to divide to form a hollow
sphere, the early blastocyst, consisting of a single layer of trophoblast
cells and the embryoblast, an inner core of cells which will form
the embryo. The trophoblast, after implantation, will form the vascular
interface with the maternal circulation. After around 2 days in the uterus, the
blastocyst is accepted by the endometrial epithelium under the influence of
estrogens, progesterone and other endometrial factors. This embedding or
implantation process triggers the ‘decidual response’, involving an expansion
of a space, the decidua, to accommodate the embryo as it grows. The invasive
trophoblast proliferates into a protoplasmic cell mass called a syncitiotrophoblast,
which will eventually form the uteroplacental circulation. By about 10 days,
the embryo is completely embedded in the endometrium.
If the ovum is fertilized and becomes
implanted, the corpus luteum does not regress, but continues to secrete
progesterone, and within 10–12 days after ovulation the syncitiotrophoblast begins
to secrete human chorionic gonadotrophin (hCG) into the intervillous
space. Most pregnancy tests are based on the detection of hCG, which takes over
the role of luteinizing hormone (LH) and stimulates the production of
progesterone, 17-hydroxyprogesterone and estradiol by the corpus luteum. Plasma
levels of hCG reach a peak between the ninth and four-teenth week of pregnancy,
when luteal function begins to fade, and by 20 weeks, both luteal function and
plasma hCG have declined.
The syncitiotrophoblast secretes
another hormone, human placental lactogen (hPL), whose plasma levels in
the maternal circulation (but not in that of the fetus) rise concomitantly with
placental growth. Its function may be to inhibit maternal growth hormone
production, and it has several metabolic effects, notably glucose-sparing and
lipolytic, possibly through its anti-insulin effects. As a result, the placenta
ensures a plentiful supply of glucose, free fatty acids and amino acids for the
fetus.
The corpus luteum synthesizes relaxin,
which relaxes the uterine muscle. The hormone is detected in the ovarian venous
drainage, is present throughout pregnancy, rising in late gestation, but is
rarely found in the plasma of non-pregnant women. Relaxin targets the pubic
symphysis, that is the point of fusion of the pubic bones, and softens this by
converting the connec- tive tissues from a hard to a more fluid consistency.
This will facilitate the widening of the pubis to allow the fetus to pass
through. Relaxin achieves this effect by increasing the secretion of two
enzymes, collagenase and plasminogen activator, both of which dissolve
collagen. In late pregnancy, relaxin may be synthesized by the myometrium, the
decidua (the mucous membrane which lines the pregnant uterus) and by the placenta.
The placenta, which takes over the
production of the hormones of pregnancy from the corpus luteum, is part of what
is termed the fetoplacental unit. The placenta attains its mature structure by
the end of the first trimester of pregnancy. Its functional unit is the
chorionic villus, consisting of a central core of loose connective tissue,
packed with capillaries which communicate with the fetal circulation. Around
the core are two layers of trophoblast, an inner layer of cytotrophoblast cells
and an outer syncytium. The placenta is not only an endocrine organ, but also
provides nutrients for the developing fetus and removes its waste products. The
fetoplacental unit produces many of the hormones released by the
hypothalamic–pituitary– gonadal axis.
Steroidogenesis
Progesterone concentrations rise
progressively during pregnancy, and a major function of the hormone is thought
to be its action, together with relaxin, to inhibit uterine motility, partly by
decreasing its sensitivity to oxytocin (Fig. 27b). The placenta lacks
17-hydroxylase and therefore cannot produce androgens. This is done by the
fetal adrenal glands, and the androgens thus formed are the precursors of the
estrogens. The placenta converts maternal and fetal dehydroepiandrosterone sulphate
(DHEA-S) to testosterone and androstenedione, which are aromatized to estrone
and estradiol.
Another enzyme lacking in the placenta
is 16-hydroxylase, so the placenta cannot directly form estriol and needs
DHEA-S as substrate. Estriol formed by the placenta (Fig. 27c) passes into the
maternal circulation, where it is conjugated in the liver to form the more
soluble estriol glucuronides, which are excreted in the urine, and levels of
estriol are used as an index of normal fetal development. If the fetus lacks a
pituitary gland, no ACTH is produced and no DHEA-S, and therefore no estriol.
The consequences of estriol deficiency are delayed labour and intrauterine
death, unless caesarean section is carried out. Such mothers are resistant to
oxytocin administration, suggesting a deficiency of oxytocin receptors, which
are normally induced at term by estradiol. Another important role of estrogens
is to stimulate the steady rise in maternal plasma prolactin. Prolactin,
which is the postpartum lactogenic hormone, may serve in pregnancy to regulate
storage and mobilization of fat, and to aid in maintaining metabolic
homeostasis during pregnancy.
