Lecture 14: Physiology of Pregnancy, Parturition, and Lactation Flashcards
The mature placenta is composed of what 3 structures?
1) Chorionic Vili
2) Intervillous Space
3) Decidua Basalis
What is considered the functional unit of the placenta and how does it increase the exchange of materials?
- Chorionic Villi
- Extensive branching greatly increases the surface area for maternal-fetal exchange
How does maternal blood flow enter the uterus and where does it go?
- Enters in pulsatile spurts through the wall of uterus via the spiral arteries
- Moves into and is trapped in the intervillous space
What is the functional capillary within the placenta?
- Intervillous space
- No capillaries are present between the maternal arterioles and venules
What are the principle factors regulating maternal blood flow?
- Maternal arterial blood pressure
- Intra-uterine pressure
- Pattern of uterine contraction
The fetal blood originates from; what do the arteries vs. veins carry?
- Fetal blood originates from 2 umbilical arteries
- Umbilical arteries carry deoxygenated blood
- Blood with significantly higher O2 and nutrient content returns to the fetus from the placenta through the single umbilical vein
The diffusion of O2 from the maternal blood into the chorionic villi of the fetus causes what?
The PO2 of blood in the intervillous space to fall
Despite the relatively low PO2 of the maternal blood in the intervillous space, the fetus does not suffer from a lack of O2, why?
Fetal Hb has a much higher affinity for O2 than does maternal Hb, the fetal Hb can extract O2 from the maternal Hb
How do LDL, transferrin, hormones, and antibodies move across the placenta?
Receptor-mediated endocytosis
What is the first hormone produced by the syncytiotrophoblasts; what is it composed of; binds which receptor?
- Human Chorionic Gonadotropin (hCG)
- Composed of a common α-glycoprotein subunit (αGSU) and a hormone-speicific β-subunit, β-hCG (Ab’s are used to detect the β-subunit)
- Binds with high affinity to the LH receptor
What is the half-life of hCG like and when is it detected, when does it peak, and when does it decline?
- Longer half-life (up to 30 hours)
- Detectable within the maternal serum within 24 hr after implantation
- Serum hCG levels double every 2 days for the first 6 weeks until they peak at about 10 weeks, then decline to constant level
What is the primary action of hCG and what symptom can it cause?
- Stimulate LH receptors on the corpus luteum
- Prevents luteolysis and maintains a high level of luteal-derived progesterone production during the first 10 weeks
- Rapid increase in hCG is responsible for the nausea of morning sickness
What produces Human Placental Lactogen (hPL); what is it structurally similar to; and when is it detected and what are the levels like throughout the pregnancy?
- Produced in the syncytiotrophoblasts
- Structurally similar to growth hormone (GH) and prolactin (PRL)
- Detected by 10 days after conception and in maternal serum by 3 weeks gestation
- Maternal serum levels rise progressively throughout the remained of the pregnancy
What is the function of hPL?
- Antagonistic action to insulin, contributing to the diabetogenicity of pregnancy
- Increases glucose availability by inhibiting maternal glucose uptake
- Lipolytic actions help the mother to shift to the use of free fatty acids for energy
Placenta produces a high amount of Progesterone for what; what is the production like throughout the pregnancy?
- Required to maintain a quiescent myometrium and a pregnant uterus
- Production is largely unregulated and maternal progesterone levels continue to increase throughout pregnancy
- Placenta produces as much as the supply of cholesterol and the levels of choelsterol desmolase and 3β-HSD will allow
How is estrogen made by the syncytiotrophoblasts; what is it largely dependent on?
- DHEAS released from the fetal zone are converted by the syncytiotrophoblasts to either estradiol 17β and estrone or estriol
- Estrogen production is dependent on a healthy fetus
What is the major estrogen of pregnancy and why is it measured?
- Estriol
- Can be used to assess fetal well-being since its production is dependent on a healthy fetus
What are the 4 functions of estrogen during pregnancy?
1) Increase uteroplacental blood flow
2) Enhance LDL receptor expression in syncytiotrophoblasts
3) Induce prostaglandins and oxytocin receptors, involved in parturition
4) Increase the growth and development of the mamary glands
What provides the cholesterol to the syncytiotrophoblasts for the production of progesterone and what enzymes are involved in this pathway?
- Maternal liver provides the cholesterol which is sent into circulation as VLDL –> LDL and can be taken up by syncytiotrophoblasts via receptor-mediated endocytosis
- Cholesterol converted by CYP11A1 (P450scc) to Pregnenolone and then to Progesterone by 3β-HSD
What is the function of the high levels of estrogen being secreted just before ovulation in the late follicular phase?
- Promotes growth of the uterine endometrium and induces expression of the progesterone receptor
- Induces the LH surge, which induces meiotic maturation of the oocyte and ovulation of the cumulus-oocyte complex
The ovary in the midluteal phase is secreting large amounts of?
Progesterone
What is Histotrophic nutrition and what stimulates it?
- Progesterone stimulates secretion from uterine glands, which provide nutrients to the embryo
- Important mode of maternal-to-fetal transfer of nutrients dor about the 1st trimester of pregnancy, after which it is replaced by hemotrophic nutrition
What affect does Progesterone have on myometrial contractions, uterine motility and the release of paracrine factors that lead to menstruation?
- Inhibits propagation of myometrial contractions
- Prevents the release of paracrine factors that lead to menstruation
- Reduces uterine motility
What induces the “window of receptivity” of the uterine endometrium and what is this?
- Progesterone
- Receptive phase associated with increased adhesivity of the endometrial epithelium
- Formation of cellular extensions on the apical surface of endometrial epithelia
- Increased expression of adhesive proteins and decreased expression of antiadhesive proteins in the apical cell membrane
How is hCG able to be trasnsported to the ovary and what is its function there?
- Spiral arteries extend to the basal lamina of the surface
- hCG rescues the corpus luteum of the ovary
How are high levels of estrogen and progesteron able to be maintained early on and later into the pregnancy?
- Early in 1st trimester, hCG rescues the corpus luteum, which is the major source
- By week 8 of gestation, placenta becomes the major source through the coordinated biosynthetic activity of the maternal-placental-fetal unit
The placenta is an imperfect organ, what is it lacking; how does the maternal-placental-fetal unit overcome this?
- Cannot manufacture adequate cholesterol; mother supplies most of the cholesterol as LDL
- Lacks 17α-hyroxylase and 17,20-desmolase activity needed from synthesizing estrone and estradiol
- Lacks 16α-hydroxylase that is needed to synthesize estriol
- Fetal adrenal gland and liver supply the 3 enzymes lacking in the placenta
Why is the fetus unable to synthesize estrogens and why is this good?
- Lacks 3β-HSD and aromatase, which catalyze the last 2 steps in the production of estrone, precursor of estradiol and needed for estriol
- Prevents fetus from being exposed to high levels of hormone that are needed by the mother, not the fetus
How is the fetus able to greatly reduce the biological activity of necessary steroid intermediates; which hormones; what happens once they move back to the placenta?
- Conjugates them to sulfate
- As pregnenolone moves from the placenta to fetus, is sulfated
- DHEA and 16α-hydroxy-DHEA are also sulfated
- When DHEA-S and 16α-hydroxy-DHEA-S move to the placenta a sulfatase removes the sulfates, and the placenta can complete the process of steroidogenesis, exporting the hormones to the mother
What happens to maternal blood volume during pregnancy; what mediates this change?
- Starts increasing 1st trimester, expands rapidly 2nd trimester, slows down 3rd trimester, and then plateaus during last several weeks
- Increase is mainly mediated by increased aldosterone
How are the # of oxytocin receptors increased; where are they increased?
- Estrogen increases the # of oxytocin receptors in the myometrial and decidual tissues of pregnant women
- Uterus is insensitive to oxytocin until around 20 weeks of gestation
What reflex causes the release of oxytocin and what kind of contractions does it produce and how is this related to prostaglandins?
- Stretch of the cervix (Ferguson Reflex)
- Stimulates powerful contractions that sustain labor.
- Do NOT initiate the rhythmic uterine contractions characteristic of the onset of labor, this is prostaglandins job
- Once labor is initiated, maternal oxytocin is released in bursts and the frequency of these bursts increases as labor progresses
How is oxytocin able to act synergistically with prostaglandins?
- Binds receptors on decidual cells, thereby stimulating PGF2α production
Once labor is initiated what are the 2 positive feedback loops that help sustain it?
1) Uterine contractions stimulate prostaglandin release, which itself increases the intensity of contractons
2) Uterine activity stretches the cervix, thus stimulating oxytocin release through the Ferguson reflex
How is disease of the placenta thought to be involved in development of Preeclampsia?
- Limited blood supply to uterine arteries causes ischemia and endothelial damage leading to the release of cytokines
- Release of vasoconstricters such as Endothelian-1 and Thromboxane
- Decreased NO and Prostaglandins
- Increased ANG II sensitivity
What is the functional secretory unit of the breast and what does it consist of?
- Alveolus, which consists of:
- Secretory epithelial cells (alveolar cells) that secrete milk
- Contractile myoepithelial cells, surrounded by adipose cells
Differentiate the effects of mammogenic, lactogenic, galactokinetic, and galactopoietic hormones
Mammogenic: promote the proliferation of alveolar duct and duct cells
Lactogenic: promote initiation of milk production by alveolar cells
Galactokinetic: promote contraction of myoepithelial cells and thus milk ejection
Galactopoietic: maintain milk production after it has been established
What is the secretory pathway for milk secretion (proteins, structures involved, and pathway)?
- Milk proteins lactalbumin and casein are synthesized in ER stored in golgi
- Alveolar cells add Ca2+ and phosphate to the lumen of golgi
- Lactose synthetase (via 2 components, a galactosyl transferase and lactalbumin) in the lumen of Golgi catalyzes synthesis of lactose
- Water enters the secretory vesicle by osmosis
- Exocytosis of vesicle contents into alveolar lumen
What is the transcellular endocytosis and exocytosis pathway for immunoglobulins in milk secretion?
- Maternal immunoglobulin (primarily IgA) are taken up by endocytosis through the basolateral membrane
- Immunoglobulins transported to the apical membrane and secreted via exocytosis
- GI tract of the infant takes up these immunoglobulins, which confer temporary immunity
What is the lipid pathway for milk secretion; which lipids predominate in this pathway?
- Fats that predominate in milk (LCFA’s >16 carbons) originate from diet or fat stores
- F.A. form lipid droplets (milk lipids) which move to apical membrane
- As apical membrane surrounds the droplets and pinches off, it secretes the milk lipids into the lumen in a membrane-bound sac
What is the transcellular salt and water transportation pathway for milk secretion?
- Various transport processes at the apical and basolateral membranes move small electrolytes from the interstitial fluid into the lumen of the alveolus
- Water follows an osmotic gradient generaters primarily by lactose and to a lesser extent, by the electrolytes
What is the paracellular pathway for milk secretion?
- Salt and water can also move into the lumen of the alveolus through the tight junctions
- Cells, primarily leukocytes, squeeze between cells and enter the milk
Prolactin is structurally related to which hormone; discuss the feedback of suckling; and what high levels of prolactin lead to in terms of menses during lactation?
- Structurally related to GH
- Neural signals from suckling feedback to hypothalamus decreasing dopamine release, increasing prolactin secretion
- Feedback also decreases release of GnRH which decreases LH and FSH
- High levels of prolactin may lead to lactational amenorrhea
What is the effect of Oxytocin on lactation and how does suckling effect this hormone?
- Enhances milk ejection by stimulating contraction of the network of myoepithelial cells surrounding the alveoli and ducts of the breast (galactokinetic effect)
- Positive feedback by suckling causes more oxytocin to be synthesized and released
