(01) - Events of Early Pregnancy

Question 1

(Events of Early Pregnancy)

1. just know that it is a genetic program with differentiations and that there is also some apoptosis to give tubular structure (apoptosis in the center)

(he seems to be going over embryogenesis quite a bit… but it is in little type in the notes… so figure out what that is all about)

Question 2

(Embryo Transport to the Uterus)

1. Once fertilization the zygote detaches from what?

while undergoing cleavage divisions, begins its journey down what?

2-4. Embryo tranport accompished by what three things?

5. within the oviduct (esp ampulla) is movement fluid?
6. transport is rapid before being arrested (days) where?

this delay caused by what?

to do what?

7. subsequent transport through isthmus is rapid… but embryos of some species halted where?
8. delays at these areas due to what?

Answer 2

1. the ampullary epithelium of the oviduct

the uterus

2. muscular contraction of oviduct (alpha1 for contraction, beta2 for relaxation) –> gives waves
3. cilia beating on oviduct epi cells
4. oviductal fluid movement in response to beating cilia
5. no - to and fro (but bias for movement to uterus)
6. ampullary isthmic junction

embryonic signals to oviduct

ensure it spends enough development time in oviduct (wouldn’t survive in uterus)

7. uterotubal junction before entering uterus
8. tonic contraction of oviducatal circular smooth muscle

(what you should get from chart is that entry into uterus happens as early blastocyst or morula)

Question 3

(Regulation of Transport)

1. Regulation of transport under influence of what three things?

(steroid hormones)

2. Influence of steroid hormones varies with species

what does steroid estrogen do?

in rabbit?

(paracrine factors)

3. embryo able to exert control over oviductal transport by secreting paracrine factors - can slow (to allow development) or speed up
4. 1 in most species both embryos and unfertilized oocytes are transported into uterus…. in horse, donkey, some bats, only what are transported?
5. 2 equine embryos secrete PGE2 from compact morula stage (day 5)…. this does what?
6. In other speceis both oocytes and embryos are transported, but what?

what is responsible for this?

Answer 3

1. steroid hormones

paracrine factors

alternating Beta2 and alpha1 adrenergic stimulation

2. hastens transport

slows it

3. 1 fertilized eggs (embryos) (bypassing degnerating unfertilized oocytes retained in oviduct)
4. 2 acts locally to relax circular smooth muscle layer of the oviduct –> embryo can progress
5. entry of embryos to uterus is earlier

platelet activating factor (PAF)

Question 4

(Embyro migration within the uterus)

1. in cows and sheep (singles and some twins) develop where?

same side = ?

opposite side = ?

do they have a tendency to migrate?

they have to do this to achieve what?

2. The horse has single embryo that does what?

Answer 4

1. in the uterine horn on the same side as CL

ipsilateral

contralateral

no

maternal recognition of pregnancy

( (Although in ewes, if there are multiple ovulations off one ovary then the embryos will tend to distribute evenly)

2. migrates freely uterus until its increase in size and tonic uterine contraction lodges it at base of one of the horns

(the horse embryo MUST migrate to contact entire endometirum in order to survive)

Question 5

(Embryo Migration within the uterus) cont

3. Camelids have equal distirubtion of ovulations from right and left…. what percentage of pregnancies in left uterine horn?
4. What happens in polytoccus species such as dog, cat, pig?

thought to be what in these that causes even spacing?

embryonic signals include what?

In the sow, all embryos found where on days 5-6 post estrus?

do what by day 9?

continued migration and mixing occurs to day 12, when what happens?

Answer 5

3. >95%

(at entry into uterus at day 6, embryos from right move left at day 8-9)

4. migrate freely to achieve even spacing (to ensure adequaate placenta for support)

chemical signals from embryo, stretching of uterine wall by increaseing size –> stimulate myometrial contractions that result in even spacing

histamine, estrogens, prostaglandins

near the tips of the uterine horns

migrate and start mixing with embryos from opposite horn

they are evenly spaced

Question 6

(Hatching)

1. One function of the zona pellucida may be to prevent the embryo attaching prematurely, during its transport through the oviduct, which would result in what?

this is more likely to be problem in what?

2. Following transport into the uterus, the embryo must escape the ZP to do what?
3. This occurs at what stage?

termed what?

4. For this to occur the blastocyst (and maybe the uterine endometrium) do what?

the blastocyst expands and contracts, probably under the influence of what?

5. this combo results in what?
6. The cells of the trophoblast can now do what?

Answer 6

1. a “tubal pregnancy”

primates and rodents (early and aggressively invasive approach to implantation)

2. form a placenta (and to benefit from supportive uterine secretions prior to implantation)
3. expanded blastocyst stage

blastocyst or zona hatching

4. secretes enzymes (plasmin, trypisin) that weaken the zona

prostaglandin E

5. splitting of the zona - and the blastocyst deforms and squeezes through the gap
6. interact directly with those of the uterine epithlium (endometrium)

Question 7

(Conceptus Elongation)

1. Following hatching, the embryos of many species go through an exponential growth phase of elongation involving the extraembryonic membranes (trophoblast and extraembryonic endoderm at this stage).

commences on what day in ewe and sow?

what day in cow?

2. this process is directed by what?

Answer 7

1. day 11

day 14 or 15

2. products of endometrium secreted into the histotroph

(embryos maintined in-vitro after hatching do not elongate.)

Question 8

(Conceptus Elongation)

1. The bovine embryo on day 13 is spherical and approximately 3 mm in diameter. By day 17 it is a 25 cm (10”) filamentous structure and by day 18 has extended into the opposite uterine horn. This is due to what?
2. The process in the pig is incredibly rapid. At day 10 they are 2 mm spheres, on day 11-12 10 mm cylinders and they then start elongating at 30-40 mm/hr, reaching lengths of 100 cm (~39”) by day 16. Early lengthening (<20 cm) comes about largely through what?
3. these elongation are aimed at having the trophoblast doing what?
4. How is the horse different?

Answer 8

1. hyperplasia of cells in the trophoblast

(the embryo proper remaining in the horn ipsilateral to the CL (i.e. the horn it entered following transport down the oviduct).)

2. cellular remodeling and reorganization rather than hyperplasia. Later, hyperplasia takes over.
3. contacting as much uterine endo as possible (to ensure maternal recognintion of pregnancy)
4. enclosed in its capsule, does not elongate in early pregnancy, it ensures contact with a large part of the the endometrium by moving around.

Question 9

(Maternal recognition of pregnancy)

1. What is a requirement for establishment of pregnancy?

this does what?

2. In most species we deal with (those classified as having short cycles) how does luteal phase compare to pregnancy duration?

the lifespan of the CL is also less than the time needed for what?

thus what is needed?

what term is used for the process by which the emryo signals its presence to the maternal system and prolongs the life of the CL?

3. The embryo can prolong CL by doing either…

Answer 9

1. Progesterone production by the CL

creates a uterine environment in which the early embryo can survive and establish itself

(undergoing implantation with the development of a placenta, fetal development and eventually birth.)

2. considerably shorter

development of another structure (placenta) that can take over progesterone secreting (in species that don’t rely on CL throughout pregnancy)

a way to prevent luteolysis

“maternal recognition of pregnancy”

3. supporting with luteotropic signal or produce antiluteolytic signal

Question 10

(Ruminants)

1. The mechanism of maternal recognition of pregnancy, and rescue of the CL, appears to be almost identical in cattle, sheep and goats.
2. In these species luteolysis is due to prostaglandin release from the uterine endometrium in response to changing the effective estradiol/progesterone ratios toward the end of the luteal phase.
3. This ratio change induces increased endometrial oxytocin receptorsand increased central oxytocin release, resulting in prostaglandin secretion. There is also the back-up system of luteal oxytocin release, and the counter-current exchange system

Question 11

(Ruminants)

(cont1)

1. within these species luteolyis is bi or unilateral?

why is this?

2. The embryonic trophoblast of these species secretes what?

Answer 11

1. unilateral (ie prostaglandin from left uterine horn needed to lyse CL on the left ovary)

Prosagladin from right horn inactivated in lungs when it circulates

(thus a single pregnancy (embryo) in these species has to exert its influence in the horn on the side of the CL (the side it’s oocyte came from). Thus they don’t migrate to the opposite horn.)

2. interferon tau (IFN-τ)

Question 12

(Ruminants)

(cont2)

1. In ewes the estrous cycle is 17 days with luteolysis at day 14-16.

The trophoblast elongates rapidly from day 11 and secretes IFN-τ from days 10-21 of pregnancy, with peak when?

2. IFN-τ acts where to do what?

Answer 12

1. day 14-16
2. endometrium to block transcription of estrogen receptors

(Without the increase in estrogen receptors there is not estrogen up-regulation of the oxytocin receptor gene thus endometrial oxytocin receptors are at low levels. Centrally released oxytocin has no receptors to act on so the pulsatile release of PGF2α from the endometrium does not occur and the CL continues to function*.)

Question 13

(Ruminants)

(cont3)

1. In the cow luteolysis occurs on around day 16 of the 21 day cycle, and maximum expression of IFN-τ occurs when?
2. The IFN-τ prevents what?
3. Thus the system in ruminants is classified as what?

Answer 13

1. days 15-18
2. up-regulation of endometrial oxytocin receptors,

(though it is currently unclear if this is indirect (via an action on estrogen receptor gene as for the sheep) or directly on the oxytocin receptor gene itself.)

3. antiluteolytic (rotects the CL by preventing release of prostaglandin)

Question 14

(Pigs)

1. The estrous cycle of the sow is how many days?

Luteolysis occurs by release of endometrial PGF2α on days what?

2. In pigs there is an endocrine-exocrine theory of maternal recognition.

This says that what?

however what happens when sow is pregnant?

3. Change in direction from endocrine to exocrine first occurs at day what?

is associated with what?

4. At least how many embryos must be present in each uterine horn to prevent luteolysis.
5. While there is a change in direction of PGF2α secretion, is there a change in its quantity?
6. Thus in the sow the mechanism is what?

Answer 14

1. 21

15 or 16

2. In the non-pregnant cycle PGF2α is secreted in an endocrine manner to the uterine vasculature from where it is transported to the CL to cause luteolysis.

However, when the sow is pregnant, the direction of PGF2α secretion changes and it is dischargedin an exocrine manner, into the uterine lumen, where it is sequestered.

3. 10-12 of pregnancy

production of estrogens from the elongating pig embryos

4. 2
5. no
6. antiluteolytic (prevents prostaglandin accessing the CL).

Question 15

(Mare)

1. estrous cycle is how long?

Luteolysis occurs with release of PGF2α on days what?

2. During early pregnancy (prior to day 16) the equine conceptus (paradoxically) produces what?

which cause what

3. An as yet unidentified conceptus product then acts on the endometrium to prevent PGF2α release.

Thus in the mare the mechanism is what?

Answer 15

1. 20-22 days

15 or 16

2. small amounts of PGF2α and PGE2

uterine smooth muscle peristalsis and the embryo moves throughout the uterus.

3. antiluteolytic (but we don’t know what it is yet)

Question 16

(Primates)

1. Here luteolysis is thought to be mediated at the level of the ovary, so it is at this level that the conceptus must act.
2. The cycle (start menses to start menses) lasts around 28 days with luteolysis occurring when?
3. On average ovulation occurs on about day 14 of the cycle (day 1 = 1st day of menses). The embryo enters the uterus 5 days after this (~day 19).

Implantation begins 2-4 days later (day 21-23).

4. Starting at about day 23, what can be found in the circulation?

this is what kind of signal in these species?

5. Thus in primates, the system for maternal regulation is what?

Answer 16

2. just prior to onset of menses
3. a chorionic gonadotropin (human chorionic gonadotropin, hCG) (produced by the trophoblast)

luteotropic

(acts directly on the CL to support it by maintaining and “LH” signal (hCG has LH-like activity) and inducing neovascularization.)

(In marmosets, immunization against hCG results in luteolysis and pregnancy failure.)

5. luteotrophic

Question 17

(Dogs and Cats)

1. These species have a long luteal phase (after sterile mating in cats). There is no current evidence for maternal recognition as described in other domestic species. However, in the pseudopregnant cat, the CL only has a natural lifespan of ~ 40 days, while gestation is around 63 days. In the late part of gestation what appears to be luteotrophic in this speceis?
2. Similarly in the dog, progesterone levels are elevated in later pregnancy vs pseudopregnancy and this is associated with increased what?

Answer 17

1. prolactin
2. prolactin levels

(But these are not really directly parallel to the situation of maternal recognition in short-cycling species.)

Question 18

(Lab Rodents)

1. Unmated animals have an ultra-short cycle with a non-functional CL that lasts 2-3 days. Sterile mating gives a pseudopregnancy that lasts 12-14 days.
   The length of gestation is 21-22 days, and requires a functional CL for 17 of these.

Function of the CL past 12 days requires the presence of what?

2. The initial rescue of the non-functional CL of the ultra-short cycle to one of pseudopregnancy is due to what?
3. The second rescue of the CL in pregnant animals turns the 12 day CL of pseudopregnancy into what?
4. This is accomplished by production of prolactin and placental lactogens by the conceptus, both of which are what?

Answer 18

1. viable embryos in the uterus
2. mating induced prolactin secretion

(Mating triggers the initial release and subsequently the hormone is released in both daytime and nighttime surges.)

3. the 17+ day CL of pregnancy
4. luteotrophic

Question 19

(Horomonal Maintenance of Pregnancy Beyond the Stage of Maternal Recognition)

Maintenance of pregnancy is dependent on adequate levels of progesterone throughout gestation. However, the source of this progesterone may change over the course of the pregnancy.

(Cow - 282 days gestation)

1. up to 150

150-250

250-term

(Bitch - 63-66 days from LH surge)

2. ?

(Sow - 114 days)

3. ?

(Goat Doe - 147-155 days)

4. ?

(Ewe - 145-150 days)

5. ?

(Llama/Alpaca (~345 days))

6. ?
7. Mare (~340 days)
8. ?

Answer 19

1. CL only

CL+ placenta

CL

2. CL throughout
3. CL throughout
4. CL throughout
5. first 55-60 - CL

60 days-term - placenta

6. CL throughout
7. first 90-100 - CL

100 days - term - placenta

(Note that when the placenta takes over progesterone production levels within the placenta may be far higher than those in the systemic circulation.

In some species the placenta produces progestagens rather than progesterone per se and these may not cross-react on a progesterone assay (depends on your assay; so you may think she has a deficiency when really things are fine).)

Question 20

should proabbly read blastocyst arrest at end