Female Reproductive Endocrinology III Flashcards
Once the sperm fertilizes the oocyte, we see the
Second meiotic division of the oocyte
This is identified by the extrusion of the second polar body, and the appearance of the female
-contains haploid chromosomes
Pronucleus
The female and male pronuclei fuse and form the
Diploid conceptus (Zygote)
Gender of the coneptus is determined by the male contribution of either an
X or Y chromosome
It is not until after the first several weeks following fertilization that the maternal neuroendocrine system recognizes
Pregnancy
As the zygote migrates downward through the oviduct and toward the uterus, it undergoes several
Mitotic divisions
Following the formation of the morula, then blastula, the embryonic cells begin to differentiate into the
- ) Outer cell layer (trophoblast)
2. ) Inner cell mass (embryo)
This differentiated structure is identified as the
Blastocyst
Within the uterus, the blastocyst undergoes compaction, and then hatches from the outer layer of remaining
Zona Pellucida
Required for the implantation of the embry into the uterine wall
The so-called zona hatching process
Generally occurs somewhere around 4-6 days following fertilization
Implantation
About 1 in 5 pregnancies result in
Spontaneous abortion
Experimental evidence indicates that suppression of the maternal immune system within the uteroplacental unit and lymph nodes proximal to this region is an important mechanism that enables
Pregnancy
Moreover, the presence of paternal alloantigens have actually been shown to induce an increase in extrathymic regulatory T cells which in turn suppress the activity of
Effector T cells
The maternal placenta is comprised of
Endometrial tissue
The fetal placenta differentiates from the
Trophoblast cells
The fetal placenta differentiates from the trophoblast cells and is known as the
Chorion
The chorion is required for the formation of the highly vascularized chorionic villi, as well as the eventual formation of the
Umbilical arteries and veins
Blood gases and urea are exchanged between the mother and fetus via
Passive diffusion
Undergo facilitated diffusion between the mother and fetus
Glucose and lactate
The placenta serves three equally important functions throughout pregnancy. What are they?
- ) Transport
- ) Immune
- ) Endocrine
Forms during the first 5 weeks of embryonic growth
Amniotic cavity
Important for the proper development of the embryonic, renal, and respiratory systemms
Amniotic fluid
The fetal stage of pregnancy begins at
Week 10
Is in essence controlled by the maternal genome, maternal nutrition, and maternal environment
Fetal growth
During the earlier embryonic stages, fetal growth is predominantly due to
Hyperplasia
After approximately 32 weeks, fetal growth is due to
Hypertrophy
During a healthy pregnancy, maternal blood volume and cardiac output rise by approximately
40%
What percentage of cardiac output is devoted to uteroplacental blood flow?
25%
The trophoblast chorionic cells secrete the protein hormone
hCG
A placental isoform of GnRH drives hCG production, and a rise in hCG can be detected beginning approximately
7-14 days post ovulation
A good clinical marker of pregnancy
hCG doubling time
Binds to the LH receptor and stimulates the corpus luteum to continue producing progesterone
-has LH like bioactivity
hCG
hCG takes over the function of pituitary LH by stimulating the corpus luteum to secrete high levels of
Progesterone
Interestingly, loss of the corpus luteum (pathologic or surgical) within the first 35 days or so of pregnancy will result in abortion without
Progesterone replacement
The loss of corpus luteum does not affect pregnancy after around
46 days
This underscores the shift in dependence from luteal to placental progesterone secretion which occurs during the
Early first trimester
In response to elevated progesterone, the hypothalamic GnRH pulse generator is disrupted, and the release of pituitary gonadotropins is
Terminated
Remember, folliculogenesis and ovulation can not occur without
FSH and LH
A clinical marker for identifying pregnancy because it can be easily detected in the
Urine of pregnant women
By the end of the third month (the end of the first trimester), the trophoblast cells of the placenta assume the majority of
Progesterone and E2 production
This switch from luteal to placental control of the hormonal regulation of pregnancy is described as the
Maternal recognition of pregnancy
As the trophoblast mass increases during gestation, we see a rise in
Placental steroidogenesis
Placental progesterone production is driven by an abundant supply of
LDLs and VLDLs
Unlike gonadal and adrenal steroidogenesis, placental steroidogenesis is not
Acutely regulated
The sustained production of progesterone and estrogens by the placenta maintains a negative feedback effect on the
Hypothalamic/pituitary production of gonadotropins
Since no appreciable FSH is present, folliculogenesis beyond early antral development is
Arrested
Contain a ratio of progesterone:estrogen that is sufficient to block LH secretion and thus prevent menstrual cycles
Oral contraceptives
Serves as the substrate for fetal estrogen production
DHEA
Maternal and fetal tissues work in concert to produce the steroid hormones (progesterone and estriol, E3) that support
Pregnancy
Ensure that numerous fetal tissues/structures develop properly
Mitosis and apoptosis
Beginning early within the first trimester, we see and increase in the production of which 4 things?
- ) The estrogens
a. ) E2
b. ) Estriol (E3)
c. ) Estrone (E1) - ) Corticotropin-releasing hormone (CRH)
After the first trimester, we see a decline in
hCG
Serum progesterone, estrogens, and CRH all peak during the
Third trimester
When present in approximately equal amounts, E2 and E3 actually antagonize activation of the
Estrogen Receptor (ER)
This is in order to prevent estrogenic actions such as
Uterine myometrial contraction
However, whenever E2 or E3 rises, we see ER dependent changes in
Gene transcription
This results in the expression of myometrial
Contractile proteins
During the terminal stage of gestation, fetal adrenal DHEAS levels rise in response to increasing
CRH
DHEAS is hydroxilated by 16a-hydroxylase. The metabolism of 16a-DHEA leads to a preferential increase in placental
E3 production
This raises the ratio of E3:E2 to approximately
10:1
This leads to the sequential activation of the ER and estrogen responsive genes which promote
Uterine contraction
What happens in the event of fetal death?
E3 plummets and E2 dominates
Another key component of parturition (birth) involves a slight drop in
Progesterone
Important fetal anabolic hormones
IGF-I and IGF-2
Stimulate maternal IGF-1 production and concomitantly upregulate the expression of IGFs in fetal tissues
Placental GH and Human placental lactogen
Maternal serum concentrations of IGF-I peak during the
Third trimester
Recall that glucocorticoid synthesis is under the control of
ACTH (corticotropin)
ACTH secretion is stimulated by
CRH
The placenta produces CRH; maternal CRH levels rise throughout pregnancy and peak at
Delivery
Placental CRH is key in a feed-forward system that is vital for governing the production of glucocorticoids which are critical for fetal
Organogenesis and maturation
Recall that CRH stimulates the anterior pituitary corticotropes to secrete
ACTH
Within the adrenal cortex (fasciculata and reticularis), ACTH promotes the secretion of
Glucocorticoids (Cortisol) and DHEAS
Upregulates the placental expression of CHR
Cortisol
A precursor for the formation of estrogens
DHEAS
This system induces a level of maternal serum cortisol, which would be detrimental to fetal health. The placenta affords a protective function against this by the expression of
11B-HSD2
Catalyzes the conversion of cortisol into the relatively inert metabolite cortisone
11B-HSD2
Exerts effects in fetal organs such as lung maturation and production of surfactant
Cortisol
During a healthy pregnancy, intravascular volume increases as much as
50%
This begins during the first trimester, with a rapid rise during the 2nd trimester, and plateaus around
Week 30
The increase in intravascular volume is controlled by several factors; noteworthy for our purposes are the effects of
Progesterone, E2, and RAS
Stimulates erythropoesis, resulting in an approximately 30% increase in RBC volume
Progesterone
Activates the RAS causing secretion of aldosterone
Placental E2
During pregnancy, there is a profound increase in H2O reabsorption and thus a decrease in serum [Na+]. This is the result of
AVP
Creatinine production remains essentially unchanged during a healthy pregnancy; however we do see an increase in
GFR
Elevated GFR can saturate
SGLT2
This SGLT2 saturation results in the non-pathologic
-seen in 50% of women during pregnancy
Glucosuria
Interestingly, the vasopresser effect of An-II is not manifested due to the counter regulatory effects of
Local vasodilators
In fact during pregnancy, we see a slight reduction in BP and a widening of
Pulse pressure (due to lower Diastolic pressure)
BP increases to prepregnancy levels at around week
36
During pregnancy, cardiac output increases by about 40% with 25-30% of this rise due to an increase in SV during
Weeks 12-24
Additionally there is around a 24% SV increase that occurs from
Weeks 25 on
Accounts for the majority of upregulation of CO that occurs during pregnancy
Increased HR
During pregnancy, Hb content is
Elevated
However, we still see a condition of physiologic anemia due to the great increase in
Plasma volume
We call this condition
Dilutional Anemia
However, O2 delivery is mintained by the increase in
Cardiac Output
Also, relative to a non pregnant woman, a vasodilatory state occurs during
Pregnancy
This aids in systemic blood flow and is also important for facilitating perfusion of the placenta which depends upon a
High flow/low pressure environment
During pregnancy, minute ventilation increases by about 30-50%, mainly due to an increase in
Tidal volume
