The Establishment of Pregnancy

Question 1

What is mammalian pregnancy?

Answer 1

• biologically, pregnancy IS THE PERIOD BTWN FERTILIZATION & BIRTH INVOLVING MAIN FEATURES OF: internal fertilization; retention of fertilized egg, embryo, fetus WITHIN female reproductive tract; direct maternal nourishment (matrotrophy)
• driven by development of LIVE BIRTH (VIVIPARITY) on to mammalian biology

Question 2

What is fecundity?

Answer 2

reproductive output of an individual over lifetime

Question 3

What are the advantages of pregnancy?

Answer 3

• protection from thermal extremes
• protection from osmotic stress
• protection from predation

Question 4

What are the disadvantages of pregnancy?

Answer 4

• increased maternal energy use
• reduced maternal mobility & FECUNDITY
• risk of injury to both mother & fetus from immunological & inflammatory responses in utero

Question 5

What are the two groups of mammals in terms of development w/in uterus & implantation?

Answer 5

• grp of animals (mostly domestic animals) where PRE-ATTACHMENT PERIOD W/IN THE UTERUS IS LONG (up to several weeks)
• grp of animals (ex: primates) where the BLASTOCYST IMPLANTS QUICKLY AFTER ENTERING THE UTERUS

Question 6

Describe long pre-attachment period:

Answer 6

• extensive extra-embryonic mb development occurs as a result of body folding to produce amnion, allantois, & chorion
• maternal recognition of pregnancy signal is produced & the maternal recognition of signal must occur BEFORE the attachment period to the uterus

Question 7

Describe quick implantation:

Answer 7

• development of extra-embryonic mbs occur after implantation w/ a different process
• MRP signal rapidly increases AFTER implantation

Question 8

Implantation in Ca?

Answer 8

• Ca zygotes take a fairly long time to reach the uterine tubes compared to other spp ex: 7-10 days
• intrauterine migration occurs from days 12-17 so blastocysts can become evenly spaced throughout each horn. fixation & implantation starts @ ~day 17.

Question 9

Implantation in Fe?

Answer 9

• limited info, but blastocysts appear to reach uterus by ~day 6. become slightly ellipsoid thereafter & hatch from zona by ~d11
• also undergo intrauterine migration & begin implantation by day 12

Question 10

Describe elongation in Ru & Sw:

Answer 10

• during embryonic disc formation, blastocyst expansion continues in Ru & Sw, first BECOMING TUBULAR & THEN FILAMENTOUS
• in the sw, the blastocyst develops from a sphere of 10-15 mm diameter to a filamentous structure of 1 mm wide by 100-200 mm long @ day 10 of development. by ~d12-15 of gestation: filamentous structure ~ 1m long

Question 11

What is elongation?

Answer 11

• despite the enormous expansion that is observed in some like the Sw, embryos can still be well spaced
• ELONGATION of any conceptus PROVIDES MAX SA OF CONTACT BTWN TROPHECTODERM/ TROPHOBLAST & MATERNAL UTERINE EPITHELIUM
• in the Bo, the elongated embryo CAN EVEN EXTEND INTO THE NON-PREGNANT UTERINE HORN
• in Eq, Car, & primates, the embryo remains spherical & does not elongate

Question 12

What is histotrophe?

Answer 12

• the secretory products of the endometrial glands : enzymes, growth factors, cytokines, hormones transported into lumen, transport proteins (ex: glucose), nutrients (ex: AAs, glucose)
• endometrial glands undergo substantial HYPERPLASIA & HYPERTROPHY during gestation to increase SA for maximum production of histotrophe (in sheep, cows, goat, pig, horse, less so in primates)
• nourish the embryo during pre-implantation period & in some spp even during post-implantation period (promote survival, development, production of pregnancy recognition factors, implantation, & placentation

Question 13

how does maternal recognition and maintenance of pregnancy work?

Answer 13

• likely all animals can detect the presence or absence of embryos in the reproductive tract
• in order for the early events of embryogenesis to continue into an established pregnancy, luteolysis must be prevented
• some animals like Ca & Fe have a luteal phase that is close enough to the duration of actual gestation regardless of embryo presence - thus, no signal is required from conceptus
• in other spp, length of luteal phase ends before embryo normally implants, this a pregnancy recognition signal must be made by the conceptus to prolong a single or a number of corpora lutea

Question 14

what is luteolysis?

Answer 14

breakdown or loss of the corpus luteum

Question 15

what can recognition signaling from the conceptus to maternal system be?

Answer 15

• LUTEOTROPHIC - hormone(s) to act on corpus luteum to maintain luteal function
• ANTI-LUTEOTROPHIC - hormone(s) prevent uterine release of luteolytic-promoting substances ex: PGF2a

Question 16

The maintenance of a functional corpus luteum to produce progesterone for..?

Answer 16

• support secretory function of endometrium, embryonic development, implantation, placentation
• be a negative feedback on hypothalamus & anterior pituitary to inhibit follicular development, ovulation
• prevent return to estrus in polyestrous spp (large & small Ru, Eq, Sw)

Question 17

What is the signal for MRP in Fe & Ca?

Answer 17

none needed

Question 18

What is the signal for MRP in Ru?

Answer 18

Interferon Tau from trophectoderm

Question 19

What is the signal for MRP in Sw?

Answer 19

Estradiol (need 2 embryos per horn) from trophectoderm

Question 20

What is the signal for MRP in Eq?

Answer 20

proteins/ embryo migration

Question 21

How does IFN tau prevent luteolysis in Ru?

Answer 21

• IFN Tau ACTS ON ENDOMETRIAL CELLS OF UTERUS & INHIBITS OXYTOCIN RECEPTOR PRODUCTION. oxytocin cannot now stimulate pulsatile PGF2a synthesis.
• IFN tau increases SECRETION OF PROTEINS FROM ENDOMETRIAL GLANDS which enter lumen & nourish the embryo

Question 22

What are the endocrine physiological mechanisms for IFN Tau?

Answer 22

evidence also that IFN-TAU CAN BE TRANSPORTED FROM UTERO-OVARIAN VEIN TO OVARIAN ARTERY & THEN TO CL
- sustain CL function to produce progesterone (upregulation of needed genes & proteins)
- prevent lytic events of any PGF2a on CL

Question 23

How is conceptus growth dependent on IFN-tau secretion?

Answer 23

IFN-tau can have PARACRINE EFFECTS ON ENDOMETRIUM TO STIMULATE CONCEPTUS ELONGATION
- stimulate production of small cytokines to be secreted by endometrium which induce growth
- induce expression of genes responsible in endometrium to uterine attachment
- stimulate endometrial gland development & function (nutrient production (ex: glucose, amino acids), & secretion)

Question 24

How does estradiol re-route PGF2a to prevent luteolysis in the sow?

Answer 24

• in non-pregnant sow: oxytocin from endometrium, posterior pituitary, & corpus luteum promote PGF2a production in endometrium which can reach the ovary (via capillaries, uterine vein) & initiate luteolysis
• in pregnant sow: estrogen (esp. 17B-estradiol) is largely the pregnancy recognition signal from the conceptus, must be secreted btwn days 11 & 15 of pregnancy, ESTRADIOL RE-ROUTES PGF2a TO UTERINE LUMEN WHERE IT IS DESTROYED - PREVENTING LUTEOLYSIS

Question 25

What are the other roles of estradiol in sow?

Answer 25

• estradiol from the conceptus btwn d15 & d25 of gestation also INDUCES EXPRESSION OF GENES IN UTERUS RESPONSIBLE FOR CONCEPTUS ATTACHMENT @ this time (OSTEOPONTIN (OPN) secreted by uterine luminal epithelium responsible for endometrial remodeling & conceptus adhesion)
• stimulates production of endometrial prolactin receptors so prolactin can bind
• promote UTERINE GLAND DEVELOPMENT & increased ION & NUTRIENT TRANSPORT FOR CONCEPTUS
• promote immune response (TOLERANCE) of progesterone-primed endometrium to implantation/attachment

Question 26

What is PGE2?

Answer 26

• estradiol from the conceptus STIMULATES UTERINE EPITHELIA TO SECRETE PROSTAGLANDIN E2 & the conceptus also begins secreting it
• PGE2 (reaches the CL from utero-ovarian vein to ovarian artery (like Tau in Ru); provides luteoprotective role in CL (maintains CL function))

Question 27

What is the importance of the Eq conceptus?

Answer 27

• removal of the eq conceptus @ various points of pregnancy (Ex: 10 or 15 days pregnancy) lengthens the time required for return to estrus (Ex: 22 & 38 days, respectively)
• eq conceptus produces estradiol & estrone in lrg amts (enhance production of uteroferrin, but do not extend CL lifespan)
• uterine PGF2a secretion appears blocked, but not sent to lumen, rather due to decreased PTGS2 (COX2) activity
• no IFN secretion by equine conceptus

Question 28

Why does trans-uterine migration of the Eq conceptus occur?

Answer 28

• during pre-attachment phase, EQ CONCEPTUS IS MOVED OVER ENDOMETRIAL SURFACE BY UTERINE CONTRACTIONS (~12-14x per day)
• endometrial production of PGF2a is significantly reduced (decreased PTGS2 (cox-2) activity & expression; due to distribution of pregnancy recognition factor(s) by conceptus to endometrial cells)
• migration of the embryo is CRITICAL

Question 29

What is attachment or implantation?

Answer 29

movement & transient attachment, followed by firm adhesion, of trophectoderm to uterine lumenal & superficial glandular epithelia

Question 30

What are the phases of attachment/implantation?

Answer 30

• Phase 1: SHEDDING OF ZP
• Phase 2: PRE-CONTACT PERIOD when blastocysts can migrate & undergo orientation w/o contact w/ epithelia. initiate pregnancy recognition signaling
• Phase 3: trophectoderm associates w/ endometrial epithelium for unstable adhesion. In Ru, initial development of microvilli begins
• Phase 4: trophectoderm firmly adheres to luminal epithelium & in some spp superficial glandular epithelium
• Phase 5: unique to spp w/ invasive implantation of blastocyst through uterine luminal epithelium into uterine stroma that becomes decidualized

Question 31

What is uterine receptivity?

Answer 31

• represents the INTERACTIONS BTWN THE DEVELOPMENTALLY COMPETENT CONCEPTUS & THE UTERINE ENDOMETRIUM
• a restricted period of the uterine cycle (PRE-CONTACT, APPOSITION, & INVASION (if pertinent); driven by actions of progesterone, estrogens, & IFN-TAU (ru))
• LOSS OF ANTI-ADHESIVE CELL SURFACE GLYCOPROTEINS CALLED MUCINS from luminal epithelial cells of the endometrium
• this “UNMASKS” surface adhesion molecules on the endometrium (SELECTINS (low affinity contacts) for initial attachment of conceptus; INTEGRINS (higher affinity contacts) & maternal ECM (osteopontin, fibronectin) for stable adhesion of conceptus)
• conceptus also has similar receptors & ECM secretion for binding to endometrium