Pregnancy, Parturition, and Contraception

Question 1

How much sperm is released into the vagina and how many reach the uterine cavity? How many arrive at the fallopian tube?

Answer 1

250,000,000 released into vagina.

100,000 reach the uterine cavity.

50 or less arrive at distal end of the fallopian tube

Question 2

After the sperm enter the fallopian tube, what happens and how long do these stages take?

Answer 2

They get delayed in the ampullary-isthmic junction where fertilization occurs (Days 1-2)

Then delayed at utero-tubal junction (2-3 days)

Egg enters uterine cavity as a morula at days 3-4, and the blastocyst implants at day 7.

Question 3

Difference between CBG and SHBG?

Answer 3

sex hormone binding globulin (SHBG; carries estrogen and testosterone)

cortisol binding globulin (CBG;carries cortisol and progesterone)

Question 4

Estrogen on CBG and SHBG levels

Answer 4

estrogen is a very potent stimulus for the production of both CBG and SHBG. Because of this, blood levels of CBG and SHBG are highest in pregnant women at term; the time at which circulating estrogens are maximally elevated.

Question 5

What is the general stepwise mechanism for steroids causing a cellular function, starting at binding?

Answer 5

1. Target cell penetration and subsequent binding to a specific cytoplasmic receptor.
2. Transfer of the steroid hormonereceptor complex into the nucleus where it binds to specific chromatin receptor sites.
3. Activation of the genome results in the transcription of new RNA.
4. The newly formed mRNAs direct the translation of specific proteins.
5. The action of the steroid hormone is then manifest by the functions of the proteins produced, whether they may be structural or enzymatic (regulatory) proteins

Question 6

Principal site of steroid inactivation?

Answer 6

Liver

Question 7

Discuss the biochemical modifications made to steroids to excrete them

Answer 7

The major chemical modifications are reduction, glucuronidation and sulfation.

Double bonds and keto groups are reduced by hydrogenation.

Glucuronic acid or sulfate are then added to the metabolite.

Reduction renders steroid hormones inactive and glucuronidation or sulfation increase the water solubility of the metabolites so they may be readily excreted in the urine.

Question 8

Where does sperm capacitation occur, and why is it important?

Answer 8

Capacitation occurs in the female reproductive tract and involves the sequential activation of a series of hydrolytic enzymes and the merging of membranes on the sperm head. This series of reactions is collectively referred to as the acrosome reaction.

The result is a sperm which is capable of (i) interacting with receptors on the zona pellucida and (ii) digesting its way through the cell layers and membranes surrounding the egg (cumulus oophorus, corona radiata, zona pellucida and vitelline membrane).

Question 9

Penetration of the vitelline membrane by the sperm initiates two important reactions:

Answer 9

1. the release of cortical granules into the perivitelline space which prevents polyspermy
2. triggering the final stages of meiosis in the oocyte. The second polar body is extruded from the egg and a haploid number of maternal chromosomes is achieved.

Question 10

When does the ovum undero its first mitotic division? (Note MITOTIC, not MEIOTIC)

Answer 10

The ovum undergoes its first mitotic division about 24 hours after penetration.

Question 11

What are the three distinguishing regions of the blastocyst and what do they lead to?

Answer 11

cytotrophoblast, outer surrounding cells: which will form the syncytiotrophoblast

inner cell mass, which gives rise to the fetus and amniotic ectoderm

hypoblast, which gives rise to the endodermal lining of the yolk sac

Question 12

Why, specifically, is progesterone absolutely required for implantation?

Answer 12

The endometrium at the site of contact, under the influence of progesterone from the corpus luteum, is transformed into the maternal placenta, the decidua. In the absence of progesterone, implantation cannot occur.

Question 13

Thus the placenta is formed by the union of what two tissues?

Answer 13

Union of fetal tissue (trophoblast) and maternal tissue (decidua).

Question 14

What does the trophoblast secrete, and why?

Answer 14

HCG is a glycoprotein hormone (38,000 mw) secreted by the trophoblast.

The major role of HCG is to maintain corpus luteum progesterone secretion, a function essential for the maintenance of pregnancy through the 7th week as calculated from the last menstrual period.

Another essential function of HCG is stimulation of testosterone secretion by the fetal testis.

Question 15

What is HPL and what is it also called?

Answer 15

Human placental lactogen (HPL) is a protein hormone (22,000 mw) which resembles both prolactin and growth hormone in structure and function.

Because of this HPL is also referred to as chorionic growth hormone and chorionic somatomammotropin.

Question 16

What does HPL do?

Answer 16

• Mobilize and metabolize maternal fat stores, resulting in insulin resistance peripherally in the mother (can lead to gestational diabetes) and glucose for the fetus by sparing protein
• Promote breast development (mammotropic action)
• Possibly ion movement for salt control

Question 17

When do we see HPL in serum?

Answer 17

HPL production starts around 6 weeks gestation with greatest production occurring in the last half of pregnancy.

At term, concentrations of HPL in plasma are highest of all the placental protein hormones.

Question 18

Immediately after implantation, HCG from the trophoblast acts on the corpus luteum to enhance progesterone secretion. What does this result in?

Answer 18

This action of HCG rescues the corpus luteum from the spontaneous regression that would have occurred in the absence of implantation. Progesterone from the “rescued” corpus luteum, in turn, signals the hypothalamus that implantation has occurred and not to initiate another menstrual cycle.

Question 19

Specifically, how does Progesterone stop another menstrual cycle?

Answer 19

Specifically, progesterone feeds back to prevent the rise in FSH which would normally initiate the next follicular phase. Thus, progesterone from
the maternal ovary is an important neuroendocrine signal for the establishment of pregnancy

Question 20

How does progesterone “quiet the uterus”

Answer 20

Decreases uterine motility in the face of the extraordinarily high levels of estrogen that circulate during pregnancy.

Progesterone acts on the uterine smooth muscle to inhibit contractility throughout pregnancy.

Progesterone also acts on the uterus and cervix to inhibit the formation of prostaglandins, agents critically involved in the events of parturition.

Question 21

Where does the progesterone come from during pregnancy?

Answer 21

During the first 6-8 weeks of gestation the corpus luteum is the major source of circulating progesterone. After 8 weeks gestation the placenta becomes the major source of blood-borne progesterone

Question 22

Estrogen works synergistically with progesterone in the development and growth of the uterus. This action serves to maintain the growth potential of the uterus for accommodating the developing fetus.

What else does estrogen do during this period?

Answer 22

• estrogen acts together with progesterone to promote breast development for lactation
• Acts to soften the elastic tissues of the pelvic ligaments and vagina in preparation for parturition
• Increases the production of steroid hormone carrier proteins by the liver
• Stimulates the production of clotting factors

Question 23

What makes estrogen during all of this stuff?

Answer 23

Prior to the 6th week of gestation estrogen originates from the mothers ovaries. After the 7th week the fetal-placental unit is the primary source of estrogen in blood

Question 24

Discuss what causes “Estrogen dominance” in the last few days of pregnancy

Answer 24

In all non-primate animals progesterone secretion declines during the last few days of pregnancy. This loss of progesterone removes the direct quieting influence of progesterone on uterine contractility and permits the unimpeded actions of estrogen. In women, a decline is not seen in the actual levels of progesterone, however, estrogen levels continue to rise at term, whereas, progesterone levels plateau. The result is an estrogen dominance

Question 25

Discuss the environment/timing around which “relaxin” is relieved

Answer 25

Under this condition the uterine musculature becomes sensitized to the actions of oxytocin via receptor up regulation. In the relative absence of progesterone, and increased estrogen, the polypeptide hormone relaxin is secreted by the placenta and corpus luteum and acts to “relax” the cervix and pelvic ligaments

Question 26

Discuss the release of prostaglandins, which occurs with relaxin, and what this causes

Answer 26

In the relative absence of progesterone, and increased estrogen, the polypeptide hormone relaxin is secreted by the placenta and corpus luteum and acts to “relax” the cervix and pelvic ligaments.

Simultaneously, prostaglandin formation in the uterus is increased and this further sensitizes the myometrium for contraction. Prostaglandins also mediate the vascular changes that are essential for the normal delivery of the fetus and placenta.

Question 27

Discuss when oxytocin begins to be secreted and what it leads to

Answer 27

Stretching of the uterus and cervix by the baby initiates the neuroendocrine reflex for oxytocin release. Oxytocin brings on a round of contractions which produce even stronger reflex signals for oxytocin release.

A positive feedback system is established whereby each successive pulse of oxytocin results in the generation of even stronger signals for oxytocin release. This positive feedback cycle culminates in the delivery of the baby.

Question 28

What is the mechanism behind estrogen-containing birth control pills

Answer 28

The action of estrogen-containing birth control pills is to interfere with the natural ovarian feedback signal of the follicular phase. The result is that the hypothalamus fails to sense that, indeed, there is a follicle which is ripe for ovulation. Because of this, there is no ovulatory surge of LH, or ovulation. No ovulation = effective birth control

Question 29

Minipills vs. Implants?

Answer 29

Minipills contain progesterone only.

Implants usually consist of six silicon capsules containing 36 mg each of the synthetic progestin, levonorgestrel or Norplant (5 years protection).

Question 30

What is DMPA contraceptive?

Answer 30

DMPA/NET-EN refers to depot-medroxyprogesterone acetate (DMPA) and norethisterone enantate (NET-EN), two long lasting injectable contraceptives administered once every two to three months.

Question 31

The ideal “pill” for contraceptive does what two things?

Answer 31

1. disguising the positive feedback signal of ovarian estrogen
2. preventing the onset of menstruation during the treatment period (breakthrough bleeding)

Question 32

Complications of estrogen only vs progesterone pills

Answer 32

Users of the progesterone-only pill have a high incidence of breakthrough bleeding, whereas, estrogen carries the very low risk of complications due to blood clotting. The latter results, in part, from the action of estrogen to increase the concentration of clotting factors in the circulation.

Question 33

As we discussed in ICR, Preecclampsia is when we see HTN and proteinuria. What are some signs and symptoms we’ll see in patients?

Answer 33

1. Severe headaches
2. Visual disturbances
3. Abdominal pain
4. Unexplained anxiety
5. Nausea and dizziness

We get worried when we see convulsions and coma

Question 34

Besides a circulating toxin, what can lead to preecclampsia (guess what I’m thinking, I know)

Answer 34

1. Insufficient blood flow to the uterus
2. Injury to mother’s blood vessels
3. Immune imbalance - inflammation
4. Poor diet
5. Magnesium and/or calcium deficiency