2-25&26-16-Physiology Of PREGNANCY, Parturition And Lactation (Lopez)-Covers Pregancy (slide 1-49)

Question 1

Clincally, males with less than ___ sperm per mL of ejaculate are considered to be infertile

Answer 1

20 million

Question 2

The female reproductive tract is an important regulator of sperm transport. Estrogen causes the cervix to produce a ___ which forms channels to aid the passage of sperm through the cervix and only motile sperm can pass through this barrier

Answer 2

Watery mucus

Question 3

This hormone causes the cervix to produce a watery mucus to aid passage of sperm through the cervix and also causes contractions of the myometrium to help proper sperm upward toward the oviduct

Answer 3

Estrogen

Question 4

Sperm must go through __ in the female repro tract before fertilization and this is a transient event that occurs largely in the oviduct and modifies spermatozoan so that it becomes capable of fertilizing the egg

Answer 4

Capacitation–> acrosome rxn is among the changes associated with capacitation

Question 5

In vivo, the sperm must breach these 3 barriers during the process of fertilization:

Answer 5

• Expanded cumulus
• Zona pellucida
• Plasma membrane of egg (aka oolemma)

Question 6

The 1st step in fertilization requires the sperm head to weave its way past the follicular cells and attach to the __ that surrounds the oocyte

Answer 6

Zona pellucida –> sperm-ZP3 (glycoprotein) interaction)

Question 7

The 2nd step in fertilization is the acrosome rxn which leads to an increase in ___ concentration inside the sperm cell that triggers fusion of the outer acrosomal membrane with the sperm cell’s plasma membrane and results in exocytosis of most of the acrosomal contents

Answer 7

Ca2+

Question 8

In the 3rd step of fertilization, the spermatozoan penetrates the ____

Answer 8

Zona pellucida

Question 9

In the 4th step of fertilization, the cell membranes of these fuse:

Answer 9

Sperm and the oocyte (egg cell) fuse

Question 10

The 5th step in fertilization is a triggering of the oocyte’s __ meiotic division and cortical rxn. It is initiated by an increase in ___ concentration inside the oocyte, there is a massive exocytosis of granules that releases enzymes to act on glycoproteins in the ZP and cause them to harden which prevents ____

Answer 10

2nd

Ca2+

Polyspermy

Question 11

The 6th step of fertilization is the oocyte completing its 2nd meiotic division. It results in the formation of the 2nd polary body which contains a __ number of unduplicated maternal chromosomes and lies close to the 1st polar body. The nucleus of the oocyte contains a __ number of unduplicated chromosomes; as its chromosomes decondense, the nucleus of this mature ovum becomes the female pronucleus

Answer 11

Haploid

Haploid

Question 12

In the 7th step of fertilization, the sperm nucleus ___ and transforms into the male pronucleus

Answer 12

Decondenses

Question 13

In the last step of fertilization, the male and female __ fuse to form a new cell, the zygote

Answer 13

Pronuclei

Question 14

Once the male and female pronuclei contact each other, the nuclear membranes break down, the chromosomes align on a common metaphase plate, and the first embryonic cleavage occurs. The mingling of chromosomes, known as ___, can be considered as the end of fertilization and the beginning of embryonic development

Answer 14

Syngamy

Question 15

The 1st week of embryogenesis occurs within the lumina of the ___

Answer 15

Oviduct and uterus

Question 16

Fertilization typically occurs on day(s) ___ of the menstrual cycle

The first 2 cleavages takes about 2 days and the embryo reaches a 16-cell ___ by 3 days

During days 4 and 5, the embryo reaches the __ stage

Implantation of the human ___ occurs about 6-7 days following ovulation

Answer 16

15 or 16

Morula

Blastocyst

Blastocyst

Question 17

During cleavage of the embryo, cells on the outer part of the morula become bound tightly together with the formation of desmosomes and gap junctions which is known as ___

Answer 17

Compaction

Question 18

During cleavage of the embryo, a cavity forms inside the morula by active transport of Na from trophoblast cells and osmosis of water, giving rise to the ___

Answer 18

Blastocyst

Question 19

During embryo cleavage, the blastocyst’s outer cells with become the ___, while some cells will remain trapped in the interior, becoming the ___

Answer 19

Trophoectoderm

Inner cell mass

Question 20

The ___ of the blastocyst is pluripotent and will ultimately form the “embryo proper”, while the ___ of the blastocyst will form the placenta and extra-embryonic tissue

Answer 20

ICM

Trophoectoderm

Question 21

___ secretions nourish the preimplantation embryo, promote growth, and prepare it for implantation

Answer 21

Uterine

Question 22

Following conception, the endometrium is primarily controlled by ___, which initially comes from the corpus luteum

The uterine glandular epithelium synthesizes and secretes several ___-dependent proteins, which may be important for the nourishment, growth, and implantation of the embryo

The presence and action of ___ may determine the extent of the implantation window

Answer 22

Progesterone

Steroid

Pinopods–> small, finger-like protrusions on endometrial cells, appear between days 19-21 of menstrual cycle, persist for only 2-3 days, development is enhanced by progesterone but inhibited by estrogens

Question 23

The ___ secretes substances that facilitate implantation. It releases immunosuppressive/immunoregulatory agents (platelet-activating factor, hCG, early pregnancy factor, immunosuppressive factor, PGE2, IL-1alpha, IL-6, IFN-alpha, leukemia inhibitory factor, and CSF)

Answer 23

Blastocyst

Question 24

___ not only acts as an immunosuppressant but also prevents menstruation by sustaining the function of the corpus luteum, signaling the mother’s body that she is pregnant

Answer 24

HCG–> 1 of the most important of the factors secreted by the trophoblast of the blastocyst, both before and after implantation; closely related to LH, sustains corpus luteum in presence of rapidly falling levels of maternal LH; an autocrine factor that promotoes growth and placental development

Question 25

During implantation, the __ of the blastocyst secretes proteases that digest the outer-lying ZP. The hatched blastocyst is able to adhere to and implant into the receptive uterine endometrium

Answer 25

Trophoblasts

Question 26

___ is initiated when the blastocyst comes into contact with the uterine wall

Answer 26

Implantation

Question 27

At the time of attachment and implantation, the trophoblasts differentiate into these 2 cell types:

Answer 27

Cytotrophoblasts and syncytiotrophoblasts

Question 28

__ is the inner cell layer of the trophoblast that proliferates rapidly and initially provide a feeder layer of continuously dividing cells

___ is the outer layer of the trophoblast that has adhesive, invasive, and endocrine functions. It secretes hCG at onset of implantation which maintains the viability of the corpus luteum of pregnancy. It also makes progesterone at sufficient levels to maintain pregnancy independently of the corpus luteum

Answer 28

Cytotrophoblasts

Syncytiotrophoblasts

Question 29

As implantation and placentation progress, __ have functions in phagocytosis and bidirectional placental transfer of gases, nutrients, and wastes

Answer 29

Syncytiotrophoblasts

Question 30

Before initiation of implantation, the ZP degenerates and is broken down by ___

Answer 30

Lytic factors –> a putative lytic factor is plasmin

Question 31

Implantation occurs in these 3 stages:

Answer 31

Apposition, adhesion, and invasion

Question 32

This stage of implantation is the earliest contact between the blastocyst wall, the trophoectoderm, and the endometrial epithelium. It usually occurs where there is a small crypt in the endometrium. The final correct orientation (ICM pointing toward endometrium) occurs by free rotation of ICM within the sphere of overlying trophoectoderm cells

Answer 32

Apposition

Question 33

___ is a transmembrane glycoprotein expressed at the apical surface of endometrial epithelial cells during the window of implantation and might be involved in apposition

Answer 33

MUC1

Question 34

This stage of implantation is characterized by a much stronger attachment to the endometrium, the trophoblast appears to attach to the uterine epithelium through the microvilli of the trophoblast, there are likely ligand-receptor interactions involved which may help to dislodge the decidual cells from their connection to the underlying basal lamina, which enables the blastocysts to perform the succeeding invasion

Answer 34

Adhesion

Question 35

This stage of implantation is a further establishment of the blastocyst in the endometrium. As the blastocyst attaches to the endometrial epithelium, the trophoblastic cells rapidly proliferate, and the trophoblast differentiates into the inner cytotrophoblast and outer syncytiotrophoblast

Answer 35

Invasion

Question 36

During implantation (invasion stage), long protrusions from the syncytiotrophoblasts extend among the uterine epithelial cells. These protrusion dissociate the endometrial cells by secreting ___ which interferes with the expression of cadherins and beta-catenin. These syncytiotrophoblast protrusions then penetrate the basement membrane of the uterine epithelial cells and reach the uterine stroma

Answer 36

TNF-alpha

Question 37

The __ secretes several autocrine factors, which may stimulate invasion of the endometrial epithelium, as well as proteases.

___ is an autocrine growth factor for the blastocyst, ___ proteases degrade the ECM and may control both the proliferation and invasion of the trophoblast into the endometrium

Answer 37

Trophoblast

hCG

Metalloproteases and serine proteases

Question 38

During the invasion stage of implantation: as the finger-like projections of the syncytiotrophoblast invade the endometrium, they reach the maternal blood supply and represent a primordial form of the ___ of the mature placenta

Answer 38

Chorionic villus

Question 39

___ is the maternal response to implantation and to progesterone

Answer 39

Decidualization

Question 40

___ are derived from the fibroblast-like cells within the endometrium, which maintain their progesterone receptors in the presence of progesterone

Answer 40

Decidualized stromal cells–> endometrial stroma is transformed into enlarged and glycogen-filled decidual cells

Question 41

The ___ forms an epithelial-like sheet with adhesive junctions that inhibits migration of the implanting embryo

Answer 41

Decidua

Question 42

Shortly after the blastocyst has implanted (6-7 days after fertilization), the ___ invades the decidua and break through into endometrial veins first, and then later into the arters which creates direct communication between lacunae and maternal vessels and the proliferation of cytotrophoblasts creates small mounds (i.e., primary chorionic villi)

Answer 42

Syncytiotrophoblast

Question 43

The mature placenta is composed of these 3 major structures:

Answer 43

• chorionic villi
• intervillous space
• decidua basalis

Question 44

___ represent the functional unit of the placenta and, through extensive branching, greatly increase the surface area for maternal-fetal exchange

___ arteries from the mother empty into the intervillous space, which is drained by maternal veins

Answer 44

Chorionic villi

“Spiral”

Question 45

The ___ is the major lifeline between the mother and the fetus

The ___: supplies nutrients

The ___: exchanges O2 and CO2

The ___: regulates fluid volumes and disposing of waste metabolites

The ___: synthesizes steroids and proteins that affect both maternal and fetal metabolism

Answer 45

Placenta

Fetal gut

Fetal lung

Fetal kidney

Endocrine gland

Question 46

Maternal blood enters in pulsatile spurts through the wall of the uterus and moves into the ___ toward the chorionic plate. After bathing the ___, the maternal blood drains through venous orifices in the basal plate, enters the larger maternal placental veins, and flows into the uterine and other pelvic veins

Answer 46

Intervillous space

Chorionic villi–> no capillaries are present between the maternal arterioles and venules; the intervillous space is the functional capillary

Question 47

The principial factors regulating maternal blood flow in the intervillous space are:

Answer 47

Maternal arterial BP
Intra-uterine pressure
Pattern of uterine contraction

Uterine contractions attenuate arterial inflow and completely interrupt venous drainage; the volume of blood in the intervillous space actually increases, to provide continual (reduced) exchange

Question 48

The fetal blood originates from 2 umbilical arteries. ___ arteries carry deoxygenated blood, unlike systemic arteries after birth

Answer 48

Umbilical

Question 49

Blood that has obtained a significantly higher O2 and nutrient content returns to the fetus from the placenta through the single ___

Answer 49

Umbilical vein

Question 50

What are 2 important functions of the amniotic fluid?

Answer 50

• serves as a mechanical buffer protecting the fetus from external, physical insults
• fetus excretes waste products through it

Question 51

TRANSPORT OF GAMETES

Following ovulation, the __ of the fallopian (uterine) tube sweep over the ovarian surface and pick up the cumulus-oocyte complex

Spermatozoa present in the male ejaculate enter the vagina near the cervix and must reach the ___ of the oviduct where fertilization occurs

Answer 51

Fimbriae

Ampulla

Question 52

Regarding gas movement across the placenta, the maternal blood coming into the intervillous space has a gas composition similar to that of ___

Answer 52

Systemic arterial blood

Question 53

Regarding gas movement across the placenta, the diffusion of O2 from the maternal blood into the chorionic villi of the fetus causes the PO2 of the blood in the intervillous space to ___

Answer 53

Fall–> despite the relatively low PO2 of the maternal blood in the intervillous space, the fetus does not suffer from a lack of O2 (fetal Hb has a much higher affinity for O2 than does maternal Hb, the fetal Hb can extract O2 from the maternal Hb)

Question 54

What are a couple of mechanisms of ensuring adequate fetal oxygenation?

Answer 54

• Relatively high cardiac output per unit body weight of the fetus
• Increased O2-carrying capacity of fetal blood late in pregnancy ([Hb] rises to a level 50% higher than that of the adult)

Question 55

How does urea and creatinine move across the placenta (from fetus to mother)?

How do lipid-soluble steroid hormones move across the placenta?

How does glucose move across the placenta?

Answer 55

Passive movement from fetus to mother

Simple diffusion; shuttle among the mother, placenta, and fetus

Facilitated diffusion-movement from mother to fetus

Question 56

How do AA’s move across the placenta?

How do vitamins and mineral move across the placenta?

How does LDL, transferrin, hormones (insulin), and Ab’s cross the placenta?

Answer 56

Secondary active transport

Active transport

Receptor-mediated endocytosis–> placenta takes up large molecules from the mother (uptake of these substances increases throughout gestation until just before birth)

Question 57

___ of the placenta produces several steroid and protein hormones. It helps maintain the pregnant state of the uterus, stimulate lobuloalveolar growth and function of maternal breasts, adapting aspects of maternal metabolism and physiology to support growing fetus, regulate aspects of fetal development, and regulate timing and progression of parturition

Answer 57

Syncytiotrophoblasts–> endocrine function of placenta

Question 58

The ___ makes a variety of hormones, including hCG and hPL. It also manufactures numerous amines, polypeptides (including peptide hormones and neuropeptides), proteins, glycoproteins, and steroids

Answer 58

Placenta

Question 59

hCG is the first hormone produced by syncytiotrophoblasts and is common of these subunits:

Answer 59

• Common alpha-glycoprotein subunit (alphaGSU)

- Hormone-specific beta-subunit (beta-hCG)

Question 60

Abs used to detect hCG (i.e., laboratory assays and OTC pregnancy tests) are designed to specifically detect this subunit of hCG:

Answer 60

Beta-hCG

Question 61

hCG binds with high affinity to the ___ receptor.

Answer 61

LH

Question 62

One of hCG’s primary actions is to stimulate __ receptors on the corpus luteum to prevent luteolysis and maintain a high level of luteal-derived progesterone production during first 10 weeks.

The rapid increase in ___ is responsible for the nausea of morning sickness

Answer 62

LH

hCG

Question 63

__ is AKA human chorionic somatomammotropin, is produced in the syncytiotrophoblast and structurally similar to HG and prolactin. It can be detected in the syncytiotrophoblast by 10 days after conception and in maternal serum by 3 weeks of gestation.

Answer 63

Human Placental Lactogen (hPL)

Question 64

___ is protein-anabolic and lipolytic, has an antagonistic action to insulin which contributes to the diabetogenicity of pregnancy. It increases glucose availability by inhibiting maternal glucose uptake and its lipolytic actions help the mother to shift to the use of free FA’s for energy

Answer 64

hPL

Question 65

___ express high levels of CYP11A1 (cholesterol desmolase) and a placenta-specific 3-beta-HSD type 1 (3B-HSD1) but do not express 17-alpha-hydroxylase/17,20 lyase/17,20 desmolase. These also express LDL receptors that import cholesterol from the maternal blood

Answer 65

Syncytiotrophoblasts

Question 66

The placenta produces a high amount of ___, which is required to maintain a quiescent myometrium and pregnant uterus

Answer 66

Progesterone –> released primarily into the maternal circulation

Question 67

Describe the levels of progesterone through pregnancy:

Answer 67

Progesterone levels continue to increase throughout pregnancy

Question 68

How is progesterone synthesize by the syncytiotrophoblast?

Answer 68

Receptor-mediated endocytosis of LDL –> cholesterol –> CYP11A1 enzyme and no StAR protein required –> pregnenolone –> Progesterone –> Effects in maternal compartment

Question 69

Just before ovulation, the ovary is in the late follicular stage and produces high levels of ___ which promotes growth of the uterine endometrium and induces expression of the progesterone receptor. It ultimately induces the LH surge, which induces meiotic maturation of the oocyte and ovulation of the cumulus-oocyte complex

Answer 69

Estrogen

Question 70

The events between fertilization and implantation take ~6 days to complete and implantation occurs at ~day 21 of the menstrual cycle. The ovary is in the midluteal phase and secretes large amounts of ___

Answer 70

Progesterone

Question 71

____ is an important mode of maternal-to-fetal transfer of nutrients for about the 1st trimester of pregnancy, after which it is replaced by hemotrophic nutrition

___ inhibits myometrial contraction and prevents the release of paracrine factors that lead to menstruation

Answer 71

Histotrophic nutrition

Progesterone

Question 72

___ induces the “window of receptivity” in the uterine endometrium, which exists from ~day 20-24 of the menstrual cycle

Answer 72

Progesterone

Question 73

The ___ phase is associated with increased adhesivity of the endometrial epithelium and involves the formation of cellular extensions on the apical surface of endometrial epithelia, along with increased expression of adhesive proteins (integrins and cadherins) and decreased expression of antiadhesive proteins (mucins) in the apical cell membrane

Answer 73

Receptive

Question 74

Describe uterine vascularization at the time of implantation:

Answer 74

It is well-vascularized –> spiral arteries extend to the basal lamina of the surface epithelium and give rise to rich capillary beds and lacunae

The extensive bloody supply immediately adjacent to the surface epithelium plays a critical role in capturing embryonic hCG and transporting hCG to the ovary, where it rescues the corpus luteum. THe endometrial bloody supply is also important for efficient delivery of progesterone to the endometrium

Question 75

During pregnancy, __ and __ rise to levels that are substantially higher than their peaks in a normal cycle

Answer 75

Progesterone and estrogen

• maternal levels of progesterone and estrogen all increase and reach concentrations substantially higher than those achieved during a normal menstrual cycle
• Elevated levels are necessary for maintaining pregnancy (progesterone reduces uterine motility and inhibits propagation of contractions)

Question 76

Early in the 1st trimester, the corpus luteum is the major source of progesterone and estrogen. By itself, the corpus luteum is not adequate to generate the very high steroid levels characteristic of late pregnancy and by 8 weeks, the ___ becomes the major source of theses steroids

Answer 76

Placenta–> the developing placenta itself augments its production of progesterone and estrogens and continues to produce large quantities of estrogens, progestins, and other hormones throughout gestation. Estriol is a major estrogen during pregnancy

Question 77

The placenta itself cannot manufacture adequate cholesterol and lacks the enzymes 17alpha-hydroxylase and 17,20-desmolase needed for synthesizing estrone and estradiol. It also lacks 16-alpha-hydroxylase needed to synthesize estriol. The maternal-placental-fetal unit overcomes these placental limitations in these 2 ways:

Answer 77

• Mother supplies most of the cholesterol as LDL particles

- Fetal adrenal gland and liver supply the 3 enzymes lacking in the placenta

Question 78

The fetus does not synthesize estrogens without assistance due to lack of ___enzymes which catalyze the last 2 steps in the production of estrone, the precursor of estradiol

Answer 78

3B-HSD and aromatase –> both are also necessary to synthesize estriol

-The fetus should NOT synthesize estrogens without assistance–> if it did, it would expose itself to dangerously high levels of hormones that not needed by the fetus, but by the mother (problem that is overcome by the maternal-placenta unit)

Question 79

Since the fetus lacks 3B-HSD and aromatase, it never makes anything beyond ___ and ___

Answer 79

DHEA and 16alpha-hydroxy-DHEA –> cannot make progesterone or any of the 3 key estrogens

Question 80

The fetus conjugates the necessary steroid intermediates to __, which greatly reduces their biological activity

As pregnenolone moves from the placenta to the fetus, it is ___

DHEA and 16alpha-hydroxy-DHEA are ___ while in the fetus

Answer 80

Sulfate

Sulfated

Sulfated

It is only when DHEA and 16alpha-hydroxy-DHEA move to the placenta that a SULFATASE removes the sulfate groups, and the placenta can complete the process of steroidogenesis and can export the hormones to the mother

Question 81

Both maternal CO and blood volume ___ during pregnancy

Answer 81

Increase

-BV starts to increase during 1st trimester, expands rapidly during 2nd trimester, rises at a much lower rate during the 3rd trimester and finally achieves a plateau during the last several weeks of pregnancy

Question 82

The increase in blood volume during pregnancy is mainly due to an increase in plasma volume through increased ___

Answer 82

Aldosterone -> the RAAS axis responds by increasing aldosterone, which augments renal reabsorption of salt and water

-Results in an increase in HR, SV, and CO

Question 83

Despite the large increase in plasma volume (during pregnancy), mean arterial pressure (MAP) usually decreases during midpregnancy and then rises during the 3rd trimester, although it normally remains at or lower than normal.

The reason for this initial fall in MAP is a decrease in ___, possibly reflecting, in part, the vasodilating effects of progesterone and estradiol

Answer 83

Peripheral vascular resistance

Question 84

The increase in CO during pregnancy reflects mainly an increase in ___

Answer 84

SV but also HR

Question 85

Increased levels of ___ during pregnancy increase alveolar ventilation

Answer 85

Progesterone –> although pregnancy has little effect on respiratory rate, it increases tidal volume markedly and thereby increases alveolar ventilation

Question 86

How does acid reflux occur during pregnancy?

Answer 86

There is prolonged gastric emptying time and decreased gastroesophageal sphincter tone–> leads to reflux

Question 87

Describe GI tract changes during pregnancy:

Answer 87

• Nausea and vomiting –> d/t elevated hCG and should resolve by weeks 14-16
• Acid reflux
• Decreased colonic motility–> increased water absorption and constipation
• Increases in demand for dietary protein, Fe, and folic acid