60: Pregnancy, Partiution, & Lactation

Question 1

1. The sperm binds to the zona _____, which is comprised of 3 glycoproteins that form a mucus-like latticework.
2. The acrosomal reaction is triggered by sperm binding to one of the glycoproteins. This _____-dependent process leads to fusion of the acrosome cap (a large organelle in the head of sperm) with the sperm cell plasma membrane (exocytosis)
3. Hydrolytic enzymes released from the ____ penetrate the zona pellucida. The sperm also rapidly oscillates/rocks to aid in the penetration process.
4. The cell membranes of the sperm and oocyte ____. The cytoplasmic portion of the sperm head and tail enter the oocyte.
5. The oocyte undergoes the cortical reaction, preventing entry of other sperm (polyspermy). This is a _____/IP3-dependent process.
6. The oocyte completes its ____ meiotic division, and a 2nd polar body is expelled.
7. The sperm head _____ and becomes the male pronucleus. The cytoplasmic portion of the sperm tail degenerates.
8. The male and female pronuclei fuse, forming the _____. The fertilized ovum thus contains 23 unpaired chromosomes from the female pronucleus plus 23 unpaired chromosomes from the male pronucleus, which align to reform a complement of 46 chromosomes (23 pairs).

Answer 1

1. The sperm binds to the zona pellucida, which is comprised of 3 glycoproteins that form a mucus-like latticework.
2. The acrosomal reaction is triggered by sperm binding to one of the glycoproteins. This calcium-dependent process leads to fusion of the acrosome (a large organelle in the head of sperm) with the sperm cell plasma membrane (exocytosis)
3. Hydrolytic enzymes released from the acrosome penetrate the zona pellucida. The sperm also rapidly oscillates/rocks to aid in the penetration process.
4. The cell membranes of the sperm and oocyte fuse. The cytoplasmic portion of the sperm head and tail enter the oocyte.
5. The oocyte undergoes the cortical reaction, preventing entry of other sperm (polyspermy). This is a calcium/IP3-dependent process.
6. The oocyte completes its 2nd meiotic division, and a 2nd polar body is expelled.
7. The sperm head condenses and becomes the male pronucleus. The cytoplasmic portion of the sperm tail degenerates.
8. The male and female pronuclei fuse, forming the zygote. The fertilized ovum thus contains 23 unpaired chromosomes from the female pronucleus plus 23 unpaired chromosomes from the male pronucleus, which align to reform a complement of 46 chromosomes (23 pairs).

Question 2

Remember that progesterone changes the uterus from a proliferative to a ______ (progesterone) uterus. The increase in basal body temp is a progesterone mediated effect in the _____. HCG binds to the same receptors as _____ & it is the main hormone that binds after the LH surge to maintain pregnancy. HCG is measured in prego tests.

Answer 2

Remember that progesterone changes the uterus from a proliferative to a secretory (progesterone) uterus. The increase in basal body temp is a progesterone mediated effect in the hypothalamus. HCG binds to the same receptors as LH & it is the main hormone that binds after the LH surge to maintain pregnancy. HCG is measured in prego tests.

Question 3

Menstrual cycle:

During the follicular phase, several primary follicles undergo further development in response to _____ and synthesize androgens, which are converted to estradiol under the influence of ____. Ultimately, one follicle fully matures and the others regress. The uterine endometrium proliferates in response to ______. Near midcyle, estradiol rises to a level that initiates positive feedback, and thus a surge in ______ release by the anterior pituitary, which results in ovulation.

During the ensuing luteal phase, the mature follicle becomes the _____, which secretes progesterone and estradiol. The uterus undergoes further proliferative and secretory changes. Unless pregnancy occurs, endometrial sloughing and menstruation eventually occur, marking the beginning of a ____ cycle.

Answer 3

During the follicular phase, several primary follicles undergo further development in response to FSH and synthesize androgens, which are converted to estradiol under the influence of LH. Ultimately, one follicle fully matures and the others regress. The uterine endometrium proliferates in response to estradiol. Near midcyle, estradiol rises to a level that initiates positive feedback, and thus a surge in LH and FSH release by the anterior pituitary, which results in ovulation.

During the ensuing luteal phase, the mature follicle becomes the corpus luteum, which secretes progesterone and estradiol. The uterus undergoes further proliferative and secretory changes. Unless pregnancy occurs, endometrial sloughing and menstruation eventually occur, marking the beginning of a new cycle.

Question 4

Fertilization typically occurs in the_____, and ~3-5 days pass as the blastocyst (~100 cells) slowly makes its way to the ____, and another ~1-2 days (7 days total) pass before _____.

Of the almost half billion of sperm deposited in the vagina, less than a hundred make their way to the ampulla of the fallopian tube.

In addition to flagella motility, sperm transport is facilitated by contractions of the uterus, cervix, and fallopian tubes in response to _______ released during the female orgasm, and prostaglandins in the male seminal fluid.

At this early stage of pregnancy, the corpus luteum continues to produce steroid hormones to ______ pregnancy as the placenta develops from trophoblasts and adjacent cells.

Answer 4

Fertilization typically occurs in the ampulla of the fallopian tube, and ~3-5 days pass as the blastocyst (~100 cells) slowly makes its way to the uterus, and another ~1-2 days (7 days total) pass before implantation.

Of the almost half billion of sperm deposited in the vagina, less than a hundred make their way to the ampulla of the fallopian tube.

In addition to flagella motility, sperm transport is facilitated by contractions of the uterus, cervix, and fallopian tubes in response to oxytocin released during the female orgasm, and prostaglandins in the male seminal fluid.

At this early stage of pregnancy, the corpus luteum continues to produce steroid hormones to maintain pregnancy as the placenta develops from trophoblasts and adjacent cells.

Question 5

Human chorionic gonadotropin (hCG) is produced in the syncytiotrophoblasts by the _____. It is closely related to LH and sustains the corpus luteum in the face of declining levels of maternal ____. In this manner, sex steroid production increases.

HCG also acts as an immunosuppresive agent, has growth-promoting activity, and promotes placental _____. HCG can be measured in the urine shortly after the blastocyst implants, and is the basis for most home _____ tests. HCG also stimulates the testes of the male fetus to produce testosterone, leading to male sex organ development.

HcG starts being produced within days of blastocyst implantation by the blastocyst. HCG rescues the corpus luteum & does what LH does. HCG gives morning ______.

Answer 5

Human chorionic gonadotropin (hCG) is produced in the syncytiotrophoblasts by the blastocyst. It is closely related to LH and sustains the corpus luteum in the face of declining levels of maternal LH. In this manner, sex steroid production increases.

HCG also acts as an immunosuppresive agent, has growth-promoting activity, and promotes placental development. HCG can be measured in the urine shortly after the blastocyst implants, and is the basis for most home pregnancy tests. HCG also stimulates the testes of the male fetus to produce testosterone, leading to male sex organ development.

HcG starts being produced within days of blastocyst implantation by the blastocyst. HCG rescues the corpus luteum & does what LH does. HCG gives morning sickness.

Question 6

During the early weeks of pregnancy, the fetus derives nutrition from the endometrial _____. Subsequently nutrition is provided by diffusion through the ______.

Answer 6

During the early weeks of pregnancy, the fetus derives nutrition from the endometrial decidua (lining). Subsequently nutrition is provided by diffusion through the placenta.

Question 7

The placenta is critical for _____ hormone synthesis. It also produces amines, polypeptides, proteins, and glycoproteins. hCG is the most important placental _____ hormone.

Also important are hormones related to growth hormone; the human somatomammotropins. They coordinate fuel economy by contributing to the conversion of glucose to fatty acids & ketones. They also promote mammary gland development in the pregnant mother.

Answer 7

The placenta is critical for steroid hormone synthesis. It also produces amines, polypeptides, proteins, and glycoproteins. hCG is the most important placental peptide hormone. hCG is simmilat to LH, think FLAT PEG.

Also important are hormones related to growth hormone; the human somatomammotropins. They coordinate fuel economy by contributing to the conversion of glucose to fatty acids & ketones. They also promote mammary gland development in the pregnant mother.

Question 8

After ~8 weeks of gestation, the coordinated activity of the maternal-placental-fetal unit maintains high levels of ____ & ________.

The placenta requires the assistance of both mother and fetus to produce _____ hormones, referred to as the maternal-fetal-placental unit. Unlike the corpus luteum, the placenta itself cannot manufacture adequate amounts of _____, the precursor for steroid hormone synthesis.

The placenta lacks two key enzymes needed for synthesis of ____ and ____. The placenta lacks a third enyzyme needed for synthesis of _____.

Answer 8

After ~8 weeks of gestation, the coordinated activity of the maternal-placental-fetal unit maintains high levels of estrogens & progesterone (reflected by a rapid rise in estriol). Remember that women get hotter when pregnant = more estrogen ese.

The placenta requires the assistance of both mother and fetus to produce steroid hormones, referred to as the maternal-fetal-placental unit. Unlike the corpus luteum, the placenta itself cannot manufacture adequate amounts of cholesterol, the precursor for steroid hormone synthesis.

The placenta lacks two key enzymes needed for synthesis of estrone and estradiol. The placenta lacks a third enyzyme needed for synthesis of estriol

Question 9

Synthesis of progesterone and the estrogens by the maternal-placental-fetal unit. The fetus lacks ______ and _______. Placenta lacks ______ and _____ (contributed by the same protein, P450c17) and ______.

The mother supplies most of the cholesterol as ___ particles. This allows the placenta to generate large amounts of ______ for export to the mother (to maintain pregnancy after the corpus luteum degenerates).

The fetal adrenal gland and liver supply the three enzymes lacking in the _____ (note the fetal adrenal glands are well-developed).

The fetus lacks the enzymes that catalyze the final steps in _____ synthesis. If the fetus alone were able to generate estrogens it would be exposed to dangerously high levels of hormones needed by the mother, not the fetus.

Answer 9

Synthesis of progesterone and the estrogens by the maternal-placental-fetal unit. The fetus lacks 3-beta- hydroxysteroid dehydrogenase and aromatase (P450arom). Placenta lacks 17-alpha-hydroxylase and 17,20-desmolase activity (contributed by the same protein, P450c17) and 16-alpha-hydroxylase.

The mother supplies most of the cholesterol as LDL particles. This allows the placenta to generate large amounts of progesterone for export to the mother (to maintain pregnancy after the corpus luteum degenerates).

The fetal adrenal gland and liver supply the three enzymes lacking in the placenta (note the fetal adrenal glands are well-developed).

The fetus lacks the enzymes that catalyze the final steps in estrogen synthesis. If the fetus alone were able to generate estrogens it would be exposed to dangerously high levels of hormones needed by the mother, not the fetus.

Question 10

Maternal response to pregnancy:

• ______ blood volume.
• MAP ______ or remains the same.
• ______ cardiac output.
• ______ alveolar ventilation due to ______ tidal volume.
• ______ demand for dietary protein, iron, & folic acid for more RBC’s.
• The uterus ______ & the breast doubles in size.
• The average weight ______ is 25-35 lbs (fetus is 8 lbs).
• BMR ______.

Answer 10

Maternal response to pregnancy:

• Increased blood volume.
• MAP decreases or remains the same (true decrease though due to increased vasculature).
• Increased cardiac output.
• Increased alveolar ventilation due to increased tidal volume.
• Increased demand for dietary protein, iron, & folic acid for more RBC’s.
• The uterus increases & the breast doubles in size.
• The average weight gain is 25-35 lbs (fetus is 8 lbs).
• BMR increases.

Question 11

Estrogen in high amounts promotes ______ & progesterone = ______ so low progesterone & high estrogen promotes max contractility. High estrogen levels are brought about by _____.

Oxytocin is released in response to _____. Myometrium contracts.

Oxytocin is not the initiator or trigger of labor. We can _____ birth giving oxytocin analouge though.

The final uterine contraction is important because it prevents _____. _______ promotes the final contraction. Hence the inition of lactation is painful.

Answer 11

Estrogen in high amounts promotes contractility & progesterone = quiets the uterus so low progesterone & high estrogen promotes max contractility. High estrogen levels are brought about by cortisol.

Oxytocin is released in response to stretch. Myometrium contracts.

Oxytocin is not the initiator or trigger of labor. We can trigger birth giving oxytocin analouge though.

The final uterine contraction is important because it prevents hemorahge. Lactation (oxytocin) promotes the final contraction. Hence the inition of lactation is painful.

Question 12

The uterus is quiescent throughout most of pregnancy due to the presence of progestogens and relaxin. During the last month, irregular “______” contractions begin, until labor when a series of regular forced contractions occur.

______ initiate contractions, and they are sustained by oxytocin and more prostaglandins. The uterus, fetal membranes and placenta produce prostaglandins (PGE2 and PGF2a) which act by a paracrine mechanism to stimulate uterine smooth muscle cells, promote formation of gap junctions between uterine smooth muscle cells which potentiates their response to _____, cause softening/thinning/dilation or effacement of the cervix.

During pregnancy, ______ increases the number of oxytocin receptors on myometrial tissue in the uterus (by ~80-fold at 36 weeks). Maternal oxytocin is released in _____ with increasing frequency during labor. This occurs in response to distension of the cervix (the Ferguson reflex).

Positive feedback loops sustain production of _____ and _____ as labor progresses. ____ is produced by the corpus luteum, placenta and decidua. Increased production during labor may help to soften/dilate the cervix. Involution of the uterus occurs after delivery in response to the changed endocrine milieu.

Answer 12

-The uterus is quiescent throughout most of pregnancy due to the presence of progestogens and relaxin. During the last month, irregular “Braxton Hicks” contractions begin, until labor when a series of regular forced contractions occur.

Prostaglandins initiate contractions, and they are sustained by oxytocin and more prostaglandins. The uterus, fetal membranes and placenta produce prostaglandins (PGE2 and PGF2a) which act by a paracrine mechanism to stimulate uterine smooth muscle cells, promote formation of gap junctions between uterine smooth muscle cells which potentiates their response to oxytocin, cause softening/thinning/dilation or effacement of the cervix.

During pregnancy, estrogen increases the number of oxytocin receptors on myometrial tissue in the uterus (by ~80-fold at 36 weeks). Maternal oxytocin is released in bursts with increasing frequency during labor. This occurs in response to distension of the cervix (the Ferguson reflex).

Positive feedback loops sustain production of prostaglandins and oxytocin as labor progresses. Relaxin is produced by the corpus luteum, placenta and decidua. Increased production during labor may help to soften/dilate the cervix. Involution of the uterus occurs after delivery in response to the changed endocrine milieu.

Question 13

_____ promotes milk let down & uterine contractility.

_____ promotes milk synthesis.

Oxytocin & prolactin are released in response to ____.

Answer 13

Oxytocin promotes milk let down & uterine contractility.

Prolactin promotes milk synthesis.

Oxytocin & prolactin are released in response to suckling.

Question 14

The hormones we do need to know:

Most of the breast is fat—the alveolar ductal system develops during puberty and even more under _____ hormones during pregnancy.

Lobuloalveolar gorwth = ____

Lactogenic = _____

_____ = promote milk let down = oxytocin stimulates contraction of smooth muscle myometrial cells

Prolactin & cortisol maintain milk production = _____ hormones

Progesterone is also an important ______ hormone. Once the ductal system has developed, progesterone acts synergistically with _____ and other hormones to cause additional growth of breast lobules, with alveoli budding and secretory characteristics.

Answer 14

The hormones we do need to know:

Most of the breast is fat—the alveolar ductal system develops during puberty and even more under mammogenic hormones during pregnancy.

Lobuloalveolar gorwth = estrogen

Lactogenic = prolactin

Galactokinetic = promote milk let down = oxytocin stimulates contraction of smooth muscle myometrial cells

Prolactin & cortisol maintain milk production = glactopoetic hormones

Progesterone is also an important mammogenic hormone. Once the ductal system has developed, progesterone acts synergistically with estrogen and other hormones to cause additional growth of breast lobules, with alveoli budding and secretory characteristics.

Question 15

The _____ is the functional secretory unit of the breast, it is organized into lobules, which drain into a _____. Groups of 15-20 ductules drain into a duct leading to the outside.

Contractile _____ cells surround each alveolus and adipose cells and promote milk let-down in response to oxytocin.

Secretory epithelial cells comprise the alveolus and secrete _____ in response to prolactin and permissive hormones, especially cortisol.

Answer 15

The alveolus is the functional secretory unit of the breast, it is organized into lobules, which drain into a ductule. Groups of 15-20 ductules drain into a duct leading to the outside.

Contractile myoepithelial cells surround each alveolus and adipose cells and promote milk let-down in response to oxytocin.

Secretory epithelial cells comprise the alveolus and secrete milk in response to prolactin and permissive hormones, especially cortisol.

Question 16

In the first couple of days you produce _____, which is not mature human milk. _____ is high in proteins & immunologic protective functions not seen in cow milk.

_____ is an emulsion of fats in an aqueous solution containing sugar (lactose), proteins (lactalbumin and casein), and electrolytes.

_____ (first-milk) provides a concentrated, low-volume form of nutrition for the neonate’s immature GI tract during the first few days of life. It has little or no _____, compared to mature human milk. It also contains protective antibodies (as does mature human milk).

Cow’s milk has a higher _____ concentration, and significantly more _____ than human milk (primarily due to casein). The delicate newborn GI tract cannot tolerate cow’s milk.

Answer 16

In the first couple of days you produce colostrum, which is not mature human milk. Colostrum is high in proteins & immunologic protective functions not seen in cow milk.

Milk is an emulsion of fats in an aqueous solution containing sugar (lactose), proteins (lactalbumin and casein), and electrolytes.

Colostrum (first-milk) provides a concentrated, low-volume form of nutrition for the neonate

Question 17

______ inhibits regular milk production before partuation.

The presence of estrogen & progesterone are critical for breast development during pregnancy, but they ___ the actual secretion of milk. The sudden loss of these steroids after delivery allows ____ to exert its lactogenic effect.

_____ maintains milk production after partuition.

While a woman is _____, it protects her from becoming pregnant again.

Answer 17

Progesterone (& estrogen) inhibits regular milk production before partuation.

The presence of estrogen & progesterone are critical for breast development during pregnancy, but they prevent the actual secretion of milk. The sudden loss of these steroids after delivery allows prolactin to exert its lactogenic effect.

Prolactin maintains milk production after partuition.

While a woman is lactating, it protects her from becoming pregnant again.

Question 18

Effect of suckling on the release of prolactin, oxytocin, and gonadotropin-releasing hormone (GnRH).

Suckling has four effects:

1. It stimulates sensory nerves, which carry the signal from the breast to the _______ where they synapse with neurons that carry the signal to the brain.
2. In the ______ nucleus of the hypothalamus, the afferent input from the nipple _____ neurons that release dopamine (DA). DA normally travels via the hypothalamic-portal system to the anterior pituitary where it inhibits prolactin (PRL) release by lactotrophs. Thus, _____ of DA release leads to an _____ in prolactin release.
3. In the supraoptic and paraventricular nuclei of the hypothalamus, the afferent input from the nipple triggers the production and release of _____ from the posterior pituitary.
4. In the preoptic area and arcuate nucleus, the afferent input from the nipple _____ GnRH release. GnRH normally travels via the hypothalamic-portal system to the anterior pituitary, where it stimulates the synthesis and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Thus, _____ GnRH release inhibits FSH and LH release, and thereby inhibits the ovarian cycle in lactating females.

Answer 18

Effect of suckling on the release of prolactin, oxytocin, and gonadotropin-releasing hormone (GnRH).

Suckling has four effects:

1. It stimulates sensory nerves, which carry the signal from the breast to the spinal cord where they synapse with neurons that carry the signal to the brain.
2. In the arcuate nucleus of the hypothalamus, the afferent input from the nipple inhibits neurons that release dopamine (DA). DA normally travels via the hypothalamic-portal system to the anterior pituitary where it inhibits prolactin (PRL) release by lactotrophs. Thus, inhibition of DA release leads to an increase in prolactin release.
3. In the supraoptic and paraventricular nuclei of the hypothalamus, the afferent input from the nipple triggers the production and release of oxytocin from the posterior pituitary.
4. In the preoptic area and arcuate nucleus, the afferent input from the nipple inhibits GnRH release. GnRH normally travels via the hypothalamic-portal system to the anterior pituitary, where it stimulates the synthesis and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Thus, inhibiting GnRH release inhibits FSH and LH release, and thereby inhibits the ovarian cycle in lactating females.

Question 19

Partuition is initiated by ____

Answer 19

Partuition is initiated by cortisol

Question 20

Implantation normally occurs _ - _ days after ovulation.

Answer 20

Implantation normally occurs 6 - 7 days after ovulation.

Question 21

Human placenta has a very high ____ enzyme activity that converts androgens to estrogens but lacks the ability to produce the androgen substrate. ____ and its ____ derivative are produced by fetal adrenal for this purpose.

Answer 21

Human placenta has a very high aromatase enzyme activity that converts androgens to estrogens but lacks the ability to produce the androgen substrate. DHEA-S and its 16-hydroxylated derivative are produced by fetal adrenal for this purpose.

Question 22

The lactation reflex occurs in response to a baby suckling, which produces a surge of ____ secretion and milk ejection. This reflex can be conditioned by stimuli such as the sound of a baby crying.

Answer 22

The lactation reflex occurs in response to a baby suckling, which produces a surge of oxytocin secretion and milk ejection. This reflex can be conditioned by stimuli such as the sound of a baby crying.

During suckling, stimulation of receptors on the nipples increases neural input to both the supraoptic and paraventricular nuclei. Activation of these nuclei leads to the release of oxytocin and neurophysin from secretion granules in the posterior pituitary gland. Suckling does not stimulate the secretion of appreciable amounts of ADH.

Question 23

Antagonism of progesterone’s effects, dilation of the cervix, and oxytocin all increase uterine smooth muscle ____ and will facilitate contractions and onset of ____.

PGE2 strongly ____ uterine smooth muscle contraction and is formed in increasing rate by the placenta late in gestation.

Answer 23

Antagonism of progesterone’s effects, dilation of the cervix, and oxytocin all increase uterine smooth muscle excitability and will facilitate contractions and onset of labor.

PGE2 strongly stimulates uterine smooth muscle contraction and is formed in increasing rate by the placenta late in gestation.

Question 24

The placenta secretes both ____ and ____ from the trophoblast cells.

Answer 24

The placenta secretes both estrogen and progesterone from the trophoblast cells.

Question 25

Testosterone stimulates the cellular functions of bone that lead to bone ____. Testosterone secretion from the interstitial cells declines with age, but it continues at sufficient levels to stimulate bone formation throughout a man’s lifetime. Conversely, estrogen production in women ____ after menopause, leaving the bones without the stimulatory effect of estrogen. As a result, osteoporosis is common in women after ____.

Answer 25

Testosterone stimulates the cellular functions of bone that lead to bone formation. Testosterone secretion from the interstitial cells declines with age, but it continues at sufficient levels to stimulate bone formation throughout a man’s lifetime. Conversely, estrogen production in women falls after menopause, leaving the bones without the stimulatory effect of estrogen. As a result, osteoporosis is common in women after menopause.