(03-02) Parturition Flashcards
(Parturition)
1st page (220) is small print but maybe look at it anyway
(Determining the Day of Parturition)
- Time of birth (day of gestation) might be determined by what?
- Most research on what causes time of birth has been done in sheep. In this species it appears to be what that determines the time of birth?
Here, absence of fetal pituitary gives what?
- In species like rabbits, rodents and marsupials, fetal decapitation has what effect on time of birth?
- How about in primates?
- Thus across species there currently seems to be a continuum from total fetal control to mostly maternal control. Further study may slide more and more of these into the fetal control category.
- fetus, the mother, or both
(It seems that in different species all of these strategies are used.)
- the fetus (through maturation of the fetal hypothalamo-pituitary-adrenal axis.)
prolonged gestation (often resulting in fetal death in-utero after the normal time of birth.)
- little to none (hus these species have been considered to be totally under maternal control.)
(However, evidence is accumulating that for at least some of these (marsupials) the fetus does exert control.)
- Both fetal and maternal factors appear to be involved
(Hormonal Factors Involved in Late Pregnancy and Parturition)
(Progesterone and Estrogen)
Both have indirect effects on uterine contractility.
- Progesterone is important in maintaining what?
2-6. does this by doing what five things?
- the absence of uterine contractions (uterine quiescence).
- *preventing formation of estrogen receptors
*preventing gap junction formation between myometrial cells
*reducing uterine innervation so that β-adrenergic influences, which are relaxant, predominate
*prevents oxytocin and prostaglandin receptor formation
*prevents action of relaxin to soften cervix
(Hormonal Factors Involved in Late Pregnancy and Parturition)
(Progesterone and Estrogen)
- Estrogens do what?
by doing what four things?
- promote uterine contractility
*induce receptors for uterotonic agents such as oxytocin, α-adrenergics and prostaglandins
*inhibit receptors for uterine relaxants such as β-adrenergics
*induce gap junctions between myometrial cells - promotes coordination and propagation of contractions
*promote synthesis of prostaglandins in animals that have had prior exposure to progesterone
(Hormonal Factors Involved in Late Pregnancy and Parturition)
(Prostaglandins)
- PGF2α is important for luteolysis and to synergize with what in promoting uterine contraction?
- PGE2 also stimulates what?
and is involved in remodeling what?
- formation stimulated by what?
- oxytocin
- uterine contraction
cervix prior to birth
- oxytocin
(Hormonal Factors Involved in Late Pregnancy and Parturition)
(Relaxin)
- In rat,pig,human the primary source during pregnancy is what?
- In catdoghorserabbit it is the what?
- In species where it comes from the CL, it is usually released in association with what?
- The cause of release from placental sources is unknown, but can occur at any time, not just at luteolysis.
- Receptors are found in the cervix, uterus, mammary gland and other tissues.
- Acts on connective tissue of the cervix and pelvic ligaments to cause softening and relaxation.
- In humans its blood levels peak much earlier in gestation (parallels HCG) and it may have no role in what?
- the CL
- placenta
- luteal regression (generally in the last 2 days of gestation (pig, rat).)
- cervical remodeling prior to parturition.
(Hormonal Factors Involved in Late Pregnancy and Parturition)
(oxytocin)
- acts in what three ways?
- Marked increase in oxytocin receptor number occurs near term in all species which acts to increase tissue responsiveness
- Increased expression of oxytocin receptors is due to an increase in what?
in rabbits,rodents,carnivores this is due to what
- *causes myometrial contractions
*causes release of PGF2α from uterine endometrium
*causes release of PGE2 from mucosa of the cervix
- he estradiol/progesterone (E/P) ratio.
decline in progesterone level and increase in estrogen
(In other species progesterone levels remain fairly high, and the increase in estrogen alone is sufficient to change the E/P ratio.)
(Mechanism of Parturtition by Species)
(Sheep)
- The production of progesterone from ~ day 60 is placental, the CL is no longer required.
- In this speceis what causes birth?
- The placenta secretes progesterone but for most of pregnancy cannot make estrogens why?
- The fetal adrenals mature in the last week - 10 days of pregnancy and respond to ACTH from the fetal pituitary by doin ghwat?
there are increases in what two things?
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- maturation of the fetal hypothalamo-pituitary-adrenal axis
(Hypophysectomy (removes ACTH) or disconnection of the hypothalamus and pituitary gland prevents parturition. A similar effect is seen in fetuses that are naturally anencephalic.)
- because it lacks sufficient activity of the enzyme 17α-hydroxylase
(hus cannot convert progestagens into androgens (a necessary intermediate in forming estrogens).)
- producing cortisol
pituitary ACTH secretion and in sensitivity of the adrenals to the stimulus
Mechanism of Parturition by Species
(Sheep cont)
- Increased cortisol increases prostaglandin synthase II (cox-2) in placental trophoblast (fetal) which increases what?
- The PGE2 has what two intiial actions?
- This increasesthe estradiol/progesterone ratio which does what four things (fuck you madill)
- PGE2 production
- • Placental PGE2 acts in an autocrine/paracrine manner to increase expression of the P450C17 enzyme (17α-hydroxylase) which allows conversion of pregnenolone (progestagens) to androgens which can later be converted to estrogen. This causes a surge in placental estrogen production.
• Placental PGE2 acts back (positive feedback) on the fetal hypothalamo-pituitary-adrenal axis to sustain the increase in fetal cortisol output (this bit is controversial*).
- increases oxytocin pulses from the posterior pituitary
• increases oxytocin receptors on the endometrium, myometrium and other tissues
• increases formation of gap junctions in the myometrium
(so the smooth muscle cells communicate and act in a more coordinated fashion)
• increases PGF2α formation in maternal endometrial tissue
(This combination causes the uterine contractions to gradually increase in strength and coordination.)
(Mechanism of Parturition by Species)
(Sheep cont2)
- Increased PGF2α secretion causes luteolysis (of remaining CL functionality) and release of relaxin** from the CL which does what?
- The softened cervix dilates as the fetus and fluids encased in the placenta are pushed into it.
- To this stage oxytocin release was pulsatile. With passage of the fetus into the cervix Ferguson’s reflex induces what?
- What synergizes with oxytocin to increase the force of the myometrial contractions?
- aids PGE2 in softening the cervix and pelvic ligaments.
- surge of oxytocin that causes powerful uterine contractions.
(These and muscle contractions of the abdominal wall deliver the fetus)
- prostaglandin
(Mech of parturition)
(sheep)
What causes Maturation of the Fetal Hypothalamo-Pituitary Adrenal Axis?
The signal for maturation that stimulates the fetal HPA axis and ultimately induces parturition is unknown. It could be genetically programmed, the response to stressors, or a combination. One concept is nutritional stress, where the fetus outgrows the placenta’s ability to supply it.
(Hypogycemia)
- One stressor that has been postulated is hypoglycemia.
The fetus is normally hypoglycemic in relation to the mother to allow transfer of glucose down the concentration gradient.
The fetal pituitary responds to hypoglycemia by increasing secretion of what?
This mechanism becomes more sensitive to hypoglycemia when?
This mechanism could potentially activate the HPA axis and cause what?
(Leptin)
just look at pic
- ACTH
after 135 days of gestation
the large cortisol increases that induce parturition (But it remains only a hypothesis.)
(Mechanism of Parturition by Species)
(Cows and Goats)
- Mechanism may be similar to sheep but progesterone maintaining pregnancy is from what?
- Maturation of the fetal adrenal axis and secretion of cortisol induces enzymes that convert this placental progesterone into what?
- CL
(They do have ~ 20% of progesterone from the placenta.)
- estrogen
(This is probably sufficient to cause production of endometrial PGF2α and the birth cascade.)
(Mechanism of Parturition by Species)
(Dogs and Cats)
- Progesterone is form the what throughout pregnancy in the bitch?
- The trigger for parturition in these species is unknown, though some have considered them to fit with the rabbits and rodents in having what?
- corpora lutea (corpus luteum = singular; corpora lutea = multiple)
(in the queen there is some evidence for placental production beyond day 50 (gestation 63-65 days))
- no fetal involvement in the decision
(However, if you look at the hormone profiles and consider that in dogs the length of pregnancy is often less than that of diestrus, it seems likely that the fetus(es) play a role, though this remains to be proven)
(Mechanism of Parturition By Species)
- In primates there is no reduction in what prior to labor
- he effective estrogen/progesterone ratio still needs to be altered in favor of estrogen if what are to work?
- how does this occur (fuck you madill)?
he human placenta lacks 17α-hydroxylase and so like the sheep cannot do what?
However unlike sheep, the enzyme in primates is not inducible by what?
The primate fetal adrenal has a “fetal zone” that synthesizes large quantities of androgens in response to what?
These androgens move to the placenta where they are converted to estrogens, thus changing the E/P ratio, especially locally within the placenta.
- “Functional progesterone withdrawal”
- Cortisol antagonizes many progesterone actions and the high levels of cortisol in the placenta mean that progesterone functions are reduced within the uterus, leading to a shift in what?
- The change in E/P ratio can now increase what three things
- Late in pregnancy for several days prior to labor, the low amplitude Branxton-Hicks contractions change during the night to become higher amplitude in response to what?
These increased contractions eventually (over 7-10 days) evolve into first stage labor.
- progesterone
- uterine contractile
- form androgens to produce estrogen.
cortisol (o primates need another source of androgens for conversion to estrogen)
fetal ACTH (it also has a regular “adult zone” that synthesizes cortisol).
- the local E:P ratio.
- oxytocin receptors, myometrial gap junctions, and prostaglandin synthesis
(Unlike sheep, primates also have oxytocin production locally within the uterus.)
- oxytocin secretion ( and perhaps increasing sensitivity of the myometrium to oxytocin)
(Circadian Timing of Parturition)
Many species will tend to give birth at a set time of the day, for example mares tend to give birth at night, often 10 pm to 2 am. Llamas tend to give birth during the daylight hours. Rats are most likely to give birth in the late afternoon, but if they don’t then the next most likely time is the middle of the next morning.
This is likely a function of the circadian clock.
- Action of the maternal clock sets the fetal clock. Thus the nocturnal increase in what secretion seen in primates is entrained by maternal mechanisms (not caused by but entrained)?
- It results in the increased placental estrogen production and in turn what?
- It is known that in rats the supraoptic and paraventricular nuclei of the hypothalamus, both areas containing the magnocellular neurones that synthesize oxytocin, receive direct innervation from the suprachiasmatic nucleus - the rhythm setting center of the brain.
- Δ4-androstenedione
- maternal pituitary oxytocin secretion and myometrial contractions that make themselves known at night.