Physiology of Pregnancy I

Question 1

At ovulation the oocyte is released from the follicle, and is still surrounded by a cluster of granulosa cells, called the [] containing the [].

Answer 1

At ovulation the oocyte is released from the follicle, and is still surrounded by a cluster of granulosa cells, called the cumulus oophorus containing the corona radiata.

It is carried in a stream of peritoneal fluid into the oviduct; where ciliary action of the epithelial cells lining the duct assist in catching the oocyte.

Question 2

Fertilization (fusion of the sperm and oocyte) typically occurs in the [] of the oviduct within[] hours after ovulation; yet, sperm from the male can remain viable in the female reproductive tract for about 48 hours. Additionally, sperm only acquire the ability to fertilize the oocyte when they have been exposed to secretions from the female reproductive tract, a process called [].

Answer 2

Fertilization (fusion of the sperm and oocyte) typically occurs in the upper third (ampulla) of the oviduct within 24 hours after ovulation; yet, sperm from the male can remain viable in the female reproductive tract for about 48 hours. Additionally, sperm only acquire the ability to fertilize the oocyte when they have been exposed to secretions from the female reproductive tract, a process called capacitation.

Question 3

Sequence of events asoiciated with fertilization:

Answer 3

1. capacitation
2. acrosmal reaction
3. membrane fusion
4. cortical reaction
5. completion of 2nd meitotis division
6. ZYGOTE!

Question 4

Capacitation

Answer 4

•The sperm cell weaves past follicukar cells and binds to the zona pellucida.

Question 5

Acrosomal Reaction

Answer 5

• A rise in [Ca2+] inside the sperm cell triggers teh exocytosis of teh acrosome (acrosomal reaction) which contains hydrolytic enzymes.
• Hyrdolytic enzymes contained in the acrosomal cap are released. These enzymes locally dissolve the zona pellucida. The whip like action of the tail pushes the sperm towards the oocyte membrane.

Question 6

Membrane Fusion

Answer 6

•With the head of the sperm now lying sideways, microvilli on the oocyte surround the sprem head. The two membranes fuse. The contents of the sperm cell enter the oocyte; the sperm cell membrane remains behind.

Question 7

Cortical Reaction

Answer 7

•A rise in [Ca2+] inside the oocyte triggers the cortical reaction, in which here is exocytosis of graules that previously lay immediately beneath the plasma membrane. The enzymes released lead to changes in the zona pellucida proteins, causing the zona pellucida to harden, preventing the entry of pother sperm cells.

Question 8

Completion of 2nd Meitotic Division

Answer 8

•The rise in [Ca2+] inside teh oocyte induces the completion of the oocyte’s 2nd meitotic division and the formation of the second polar body, which usually lies next to the first polar body.

Question 9

ZYGOTE!

Answer 9

• The head of the sperm enlarges to become the male pronucleus.
• The male and female pronucleus fuse.
• As the two pronuclei move together, the chromosomes replicate, pronuclear membranes break down, genetic material mixes, and the first mitotic division of the zygote is initiated.

Question 10

Answer 10

• The embryo spends the first 3 or 4 days in the oviduct, during which time several mitotic divisions occur to produce a ball of cells called the morula. During this time the uterus is being prepared to support pregnancy; as premature arrival in the uterus kills the morula. The endometrium is fully differentiated following pre-ovulatory estrogen priming and post-ovulatory exposure to progesterone. Progesterone is an absolute requirement for implantation, in terms of preparing the endometrium to accommodate the embryo.
• Once the morula moves into the uterus, it floats freely for an additional 3 to 4 days, living on endometrial secretions, and developing into a blastocyst.
• The blastocyst is a hollow ball of cells that contains two important cell types, trophoblastic cells (outer surface) and an inner cell mass, which develops into the fetus

Question 11

Answer 11

• The trophoblastic cells initiate implantation, 6 to 8 days after fertilization, and together with endometrial tissue, develop into the placenta.
• At the time of implantation, trophoblastic cells pass deep into the endometrium and fuse to form a syncytium (the syncytiotrophoblast). This attachment to the uterus triggers dramatic changes in the underlying stroma. The tissue affected by this is called the decidua. As the trophoblast cells invade the uterus, maternal cells are absorbed and lacunae (spaces) appear. The lacunae become filled with maternal blood from eroded capillaries and a slow circulation is evident by 12 days.
• Placental growth and the development of fetal circulation continues through pregnancy, in accordance with fetal development. The placenta is the region of apposition of the fetal membranes to the uterine epithelium for physiologic exchange.
• In humans all layers of the placenta are of fetal origin. The placenta has very important functions during pregnancy, especially in terms of respiratory and nutrient transfer to support the developing fetus. Additionally, hormone production by the placenta and fetus plays a role in the maintenance of pregnancy and initiation of labor.

Question 12

Cytotrophoblast

Answer 12

The cytotrophoblast (or layer of Langhans) is the inner layer of the trophoblast. It is interior to the syncytiotrophoblast and external to the wall of the blastocyst in a developing embryo.

Question 13

During pregnancy the human placenta produces several unique protein hormones as well as the steroid hormones [] and [].

Answer 13

During pregnancy the human placenta produces several unique protein hormones as well as the steroid hormones estrogen and progesterone.

As a result, the role of ovarian hormones (estrogen and progesterone) is limited to early pregnancy, as the fully developed placenta takes over in this capacity after the first trimester

Question 14

Role of Placental Steroid Hormones

Answer 14

• Elevated placental steroid hormones keep LH and FSH levels low (negative feedback). This insures ovarian quiescence which is a desirable hallmark of pregnancy.
• Elevated levels of progesterone are required throughout pregnancy because after the placenta develops and the fetus begins to grow,progesterone inhibits contractions of the uterine myometrium, contractions that would expel the fetus if progesterone levels fell. To ensure against premature onset of labor, circulating progesterone levels increase dramatically during pregnancy.

Question 15

The source of progesterone in the first trimester is the []; thereafter, the [] assumes this responsibility, and the [] is no longer required to maintain the pregnancy.

Answer 15

The source of progesterone in the first trimester is the corpus luteum; thereafter, the placenta assumes this responsibility, and the corpus luteum is no longer required to maintain the pregnancy.

•However, for reasons not entirely clear, the corpus luteum is maintained throughout the entire pregnancy. When implantation occurs (7 to 8 days after ovulation), progesterone secretion from the corpus luteum of the menstrual cycle is maximal. However, in the absence of a signal from the embryo, luteolysis would soon occur, causing menstruation and loss of the implanted embryo.

Question 16

Answer 16

Question 17

Answer 17

Question 18

Answer 18

Question 19

Answer 19

• In the absence of a signal from the embryo, luteolysis would soon occur, causing menstruation and loss of the implanted embryo.
• To prevent this, one of the first events following implantation is secretion of a hormone, human chorionic gonadotropin (hCG), that prolongs the life span of the corpus luteum.
• hCG is a glycoprotein, structurally similar to LH, that is produced by the syncytiotrophoblast, and binds to LH receptors. In this way, hCG produces all the tropic actions of LH in the corpus luteum.
• Circulating levels of hCG begin to rise within one to two days of implantation and peak at approximately 8 to 10 weeks of gestation. This luteotropic stimulus maintains the structure and secretory activity of the corpus luteum.
• The presence of hCG in the urine of women in early pregnancy is the basis for virtually all pregnancy tests which depend upon immunologic (hCG) or biologic (LH-like) activity.

Question 20

Answer 20

Question 21

Answer 21

• There are a variety of effects of pregnancy on the endocrine system of the mother. Chorionic somatomammotropin (hCS), also called placental lactogen (hPL), is a placental protein hormone that has a structure very similar to growth hormone (GH).
• The concentration of hCS increases gradually throughout pregnancy and plateaus during the last month.
• As its name implies, this hormone has both growth-promoting and lactogenic activities, but both are relatively weak.
• Two possible roles have been suggested for hCS during pregnancy.
• First, it may act on the mammary gland to induce the enzymes needed for milk synthesis.
• Second, it may produce important metabolic changes in the mother. During pregnancy, utilization of glucose by the mother decreases and she becomes relatively resistant to the hypoglycemic action of insulin. These metabolic changes may serve to shunt larger quantities of glucose to the fetus and, since similar effects can be produced by GH administration, they may be caused by increasing levels of hCS. Because pregnant women are relatively insensitive to the actions of insulin, diabetes mellitus often first becomes evident during pregnancy. Consequently, urinary glucose levels are routinely determined during pregnancy to monitor the possible development of diabetes

Question 22

Answer 22

•Other endocrine adjustments occur in the mother during pregnancy. In response to increasing levels of estrogens (produced by the placenta), synthesis of a variety of proteins in the liver is stimulated. Angiotensinogen, the renin substrate for angiotensin II production (related to the regulation of water and salt balance) is normally regulated by production of renin in response to physiologic cues. Although the amount of available angiotensinogen is not rate limiting under ordinary circumstances, an increase in its concentration during pregnancy may lead to the production of inappropriately high amounts of angiotensin II (AgII), and therefore also stimulation of aldosterone production. The result can be hypertension and edema.

Question 23

Proteins produced in the liver in greater amounts during pregnancy:

Answer 23

• angiotensinogen
• cortisol binding protein (CBG) and thyroxine binding protein (TBG)

-The increase in circulation of these proteins results in increases in total circulating levels of cortisol and thyroid hormone, respectively. However, because free levels of these hormones are still normal, and regulate biologic activity of these hormones, symptoms of Cushings syndrome and/or hyperthyroidism do not normally develop.

Question 24

Placental estrogen

Answer 24

• This estrogen differs qualitatively from those during the menstrual cycle in which 17ß-estradiol and estrone are the major estrogenic products of the follicular granulosa cells.
• In pregnancy, estriol also becomes a major estrogen in circulation, having weak estrogenic effects. In the non-pregnant female, estriol is predominately a metabolite of estradiol and estrone, formed in the liver; the ratio of estriol:estrone:estradiol in the urine is about 3:2:1. In contrast, the placenta secretes large amounts of estriol formed from fetal precursors as well as estradiol and estrone formed from predominantly maternal precursors. Thus, the urinary proportion of the three estrogens is markedly different in late pregnancy, 30:2:1.
• This large increase in urinary estriol is a measure of fetal viability, and provides a simple, non-invasive assay of fetal well-being in the latter stages of problem pregnancies.

Question 25

Answer 25

Question 26

Answer 26

* Most of the estrogen produced by the placenta is in the form of estriol (E3). There is an increasing ability of the placenta to convert DHEA from the maternal adrenal into estradiol and estrone as pregnancy advances. However, fetal DHEA contributes mostly to placental estrogen production. The placenta does not contain the enzymes 17ß-hydroxylase and C17-20 lyase, both of which are needed for the conversion of pregnenolone to DHEA. Thus, although it does have aromatase activity, the placenta cannot synthesize estrogens directly from prenenolone. However, the maternal and fetal adrenal can convert cholesterol to DHEA, which is then sulfated and secreted. Moreover, the placenta also lacks 16alpha-hydroxylase enzyme, so it is incapable of synthesizing estriol from estradiol. Most of the DHEA-sulfate is hydroxylated at the C-16 position by the fetal liver and the resulting 16alpha-OH-DHEA-sulfate is transported to the placenta. The placenta has an active sulfatase that removes the sulfate group and 16alphaOHDHEA is then converted to estriol by the same enzymes that normally convert DHEA to estradiol. * In summary, the important role of the fetus in supplying the precursor of estriol synthesis is as follows: the fetal zone of the adrenal cortex produces DHEA from pregnenolone that passes from the placenta during progesterone synthesis. DHEA is sulfated in the fetal adrenal, 16- hydroxylated in the fetal liver, and transported via the umbilical arteries back to the placenta, where it is aromatized to produce free estriol.

Question 27

Answer 27

Question 28

Answer 28

Question 29

Answer 29

Question 30

Answer 30

Question 31

Factors that may influemce initiation of parturition:

Answer 31

* relaxin * corticotrophin releasing hormone (CRH) * prostaglandin * estrogen * progesterone * fetus size

Question 32

Factors that may influemce initiation of parturition: Relaxin

Answer 32

* Produced by corpus luteum of pregnancy and placenta * Contributes to softening of cervix

Question 33

Factors that may influemce initiation of parturition: Corticotrophin Releasing Hormone (CRH)

Answer 33

* Produced by placenta * Promotes myometrial contractions by making uterus more sensitive to prostaglandins and oxytocin

Question 34

Factors that may influemce initiation of parturition: Prostaglandin

Answer 34

• Stimulates uterine contractions

Question 35

Factors that may influemce initiation of parturition: Estrogen

Answer 35

• Encourages uterine contraction

Question 36

Factors that may influemce initiation of parturition: Progesterone

Answer 36

* Inhibits uterine contraction * Estrogen encourages the uterine muscles to contract, whereas, progesterone inhibits uterine contractions. Thus, the concept has been advanced that a local progesterone block maintains pregnancy and removal of this block is responsible for the onset of parturition. Some researchers have suggested that it is not the absolute progesterone levels that are important but the ratio of estrogen to progesterone, and an increase in this ratio might initiate labor.

Question 37

Answer 37

* Regardless of the exact signal for onset of labor, there is an increased sensitivity (increased receptors) of the uterus to oxytocin at term. * Although, not thought to initiate parturition, increased levels of oxytocin clearly regulate and promote labor. The pattern of uterine contractions during labor is sustained by a neuroendocrine reflex arc involving oxytocin. - Each uterine contraction begins at the top of the uterus (the fundus) and spreads toward the cervix but is much stronger in the fundus. Uterine contractions thus force the fetus toward the cervix and the pressure of the fetus on the cervix stretches it. - Cervical stretch produces an afferent neural signal that travels up the spinal cord to the anterior hypothalamus and triggers oxytocin release. - Oxytocin then acts on the uterine myometrium to stimulate further uterine contractions. Note that each step in this pathway is stimulatory so that this circuit forms a positive feedback loop. This means that uterine contractions will continue, and increase, until the pressure to the cervix is relieved by delivery.

Question 38

Stage 1 of Labor

Answer 38

•During the first stage, the positive feedback loop just described causes the cervix to dilate from 2 cm to 10 cm in diameter. This stage usually is the longest, lasting 8 to 24 hours in a first pregnancy.

Question 39

Stage 2 of Labor

Answer 39

•Stage 2, the actual delivery of the fetus, begins once the cervix is fully dilated. Toward the end of stage 1, as the infant begins to move through the cervix, stretch receptors in the vagina activate a neural reflex that triggers contractions of the abdominal muscles. Once stage 2 has begun, these abdominal contractions which occur simultaneously with uterine contractions, greatly increase the force pushing the infant through the vagina. Stage 2 ends with delivery and usually lasts 1-2 hours.

Question 40

Stage 3 of Labor

Answer 40

•Stage 3 of labor, expulsion of the placenta, occurs 15 to 30 minutes after delivery. The uterus continues to contract for some time after delivery; this causes the placenta to first separate from the myometrium and then pass through the vagina. Separation of the placenta causes some uterine bleeding, but this is limited because continued muscular contractions of the myometrium constrict the maternal blood vessels supplying the damaged area. Oxytocin may be injected after delivery of the placenta to increase uterine contractions and help prevent hemorrhage.