Transcript Pregnancy - Washington State University

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
6 days postfertilization
1 day 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-placentalfetal unit
Fetal Adrenal
CHOLESTEROL
DHEA
Placenta
Maternal Bloodstream
CHOLESTEROL
CHOLESTEROL
PROGESTERONE
PROGESTERONE
DHEA
ESTROGENS
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.
Prepares for
birth stress,
starts
pulmonary
surfactant
production
Onset of labor
Fetal Pituitary
ACTH
Fetal adrenal
Cortisol
DHEA
Placenta
↑Estradiol production
↑CRF production
↑PG F2alpha production
↑oxytocin production
Uterine muscle
excitability
Maternal
oxytocin
induced by
cervical
stretch,
breast
stimulation
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.