Pregnancy

Sperm wars• An ejaculate containing 100-500 million spermatozoa is

deposited in the vicinity of the cervix• 1,000-5,000 reach the junction between uterus and

Fallopian tubes• 100-500 reach the vicinity of the ovum• This journey happens far more quickly than could be the

case if spermatozoa simply swam there – so the female system must facilitate sperm movement.

• Important points: Sperm competition - each spermatozoan in an individual male’s ejaculate is genetically unique, so there is a huge opportunity for Darwinian selection – furthermore, a female may mate with several males in rapid succession – taking the competition to a new level.

From Fertilization to Implantation

• At ovulation: primary oocyte completes 1st meiotic division, resulting in 1st polar body and 2ndary oocyte.

• Ovum enters Fallopian tube and lingers in the initial part, where fertilization occurs within about 3 days after ovulation. The 2nd meiotic division is completed before pronuclei fuse. There are now 2 polar bodies, which generally have no future.

• The zygote undergoes several rounds of mitosis as it travels down the Fallopian tube, becoming a hollow ball of cells called a blastocyst.

From pseudopregnancy to pregnancy

• In humans, implantation occurs 6-8 days after ovulation. The blastocyst lodges against the surface of the endometrium, adheres to it, and dissolves its way into it.

• The blastocyst now consists of an outer layer, the trophoblast, which will give rise to the placenta, and an inner cell mass that will give rise to the embryo.

hCG rescues the corpus luteum

• The implanted embryo must act quickly to rescue the corpus luteum – the lifespan of the corpus luteum would normally end about 14 days after ovulation.

• Without estrogen and progesterone, the endometrium would be shed before the embryo could establish itself. Apparently, quite a few pregnancies do end because the blastocyst fails to accomplish this rescue.

• How it works: The newly implanted trophoblast immediately begins to secrete chorionic gonadotropin (hCG), which has an effect on the corpus luteum similar to that of LH. This hormone is the basis for at-home pregnancy tests.

Implantation

1 day postfertilization6 days postfertilization

8 days postfertilization

Delayed implantation

• In species that exhibit delayed implantation, the blastocyst(s) are arrested at the 100-400 cell stage. Depending on the species, this allows the mother to – mate in the fall and start the metabolic

demands of pregnancy in the spring– Finish suckling a previous litter – Mate with multiple males, ovulating with each

mating, before starting a multipaternal pregnancy

The corpus luteum of pregnancy

• In the human pattern, hCG secretion sustains the corpus luteum for the first trimester of pregnancy. During this time the corpus luteum maintains the pregnant state by secreting estradiol and progesterone.

• By the beginning of the 2nd trimester, the placenta itself has become competent to secrete enough estrogen and progesterone to sustain the pregnancy. hCG secretion tapers off and the corpus luteum becomes nonfunctional.

• Mammalian species differ in the relative importance of the corpus luteum and the placenta in sustaining the pregnancy – in some species, the corpus luteum (or corpora lutea for multiple fetuses) persists for the entire pregnancy – in others, its role in pregnancy is trivial.

Placentation

• Trophoblast sends fingers of vascular tissue into the surrounding endometrium – these become chorionic villi. Chorionic villus biopsy is now the basis for prenatal genetic diagnosis.

• Each chorionic villus is submerged in a maternal blood sinus. All exchange of gases, nutrients and hormonal signals takes place across this maternal-fetal barrier.

Placentation

The mature placenta contains both a maternal and a fetal component. The maternal and fetal bloods do not mix.

Major hormones of pregnancy

Hormone Source Effect

hCG trophoblast Sustains corpus luteum; activates embryonic testes

Estrogens (Estrone, Estradiol, Estriol)

Corpus luteum; placenta

Sustains endometrium; stimulates breast development

Progesterone Corpus luteum; placenta

Inhibits uterine contractions; stimulates breast development

Prolactin Ant. Pituitary Promotes lactation (colostrum); inhibits uterine contractions

Placental lactogen(Chorionic somatomammotropin)

Placenta – maternal plasma levels are good measure of placental well-being

Antagonizes insulin; promotes nutrient mobilization during last trimester

Steroid synthesis by the maternal-placental-fetal unit

Fetal Adrenal

CHOLESTEROL

DHEA

Placenta

CHOLESTEROL

PROGESTERONE

DHEA

ESTROGENS

Maternal Bloodstream

CHOLESTEROL

PROGESTERONE

ESTROGENS

Estrogen and progesterone levels in maternal blood rise continuously during gestation

Placental steroid secretion begins to dominate – corpus luteum begins to shrink

This is a log scale!

Who is the timekeeper for gestation?

• In sheep: – the adrenal stimulus comes from increased ACTH secretion by

fetal brain. Corticosteroids initiate labor by inhibiting progesterone production; drop in progesterone initiates uterine contractions; hypophysectomy of fetal lambs prolongs gestation indefinitely.

• Hypothesis for humans: – rise in CRF from placenta matures fetal adrenal, leading to

increased corticosteroid levels in fetal blood. However, unlike sheep, a distinct drop in progesterone production before labor does not seem to occur in humans, but estrogen levels do rise relative to progesterone levels.

– If labor fails to occur at term, within a couple of weeks the fetus is at risk of death from placental decline – this is evidence that the placenta ‘knows’ how long gestation should last. The gestation period for anencephalic infants is typically prolonged, suggesting that the fetal brain is also involved in the decision to start labor.

Onset of laborFetal Pituitary

Fetal adrenalACTH

DHEAPlacenta

↑Estradiol production

Cortisol

↑oxytocin production

↑PG F2alpha production

↑CRF production

excitability

Uterine muscle

Maternal oxytocin induced by cervical stretch, breast stimulation

Prepares for birth stress, starts pulmonary surfactant production

We now believe that labor contractions are initiated by prostaglandin F2α and sustained by oxytocin that comes

from both the pituitary and the uterus itself

In both the lamb model and the human situation, oxytocin initiates labor contractions if administered at levels much higher than those that occur in normal labor.