The Establishment of Pregnancy Flashcards
What is mammalian pregnancy?
- 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
What is fecundity?
reproductive output of an individual over lifetime
What are the advantages of pregnancy?
- protection from thermal extremes
- protection from osmotic stress
- protection from predation
What are the disadvantages of pregnancy?
- increased maternal energy use
- reduced maternal mobility & FECUNDITY
- risk of injury to both mother & fetus from immunological & inflammatory responses in utero
What are the two groups of mammals in terms of development w/in uterus & implantation?
- 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
Describe long pre-attachment period:
- 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
Describe quick implantation:
- development of extra-embryonic mbs occur after implantation w/ a different process
- MRP signal rapidly increases AFTER implantation
Implantation in Ca?
- 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.
Implantation in Fe?
- 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
Describe elongation in Ru & Sw:
- 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
What is elongation?
- 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
What is histotrophe?
- 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
how does maternal recognition and maintenance of pregnancy work?
- 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
what is luteolysis?
breakdown or loss of the corpus luteum
what can recognition signaling from the conceptus to maternal system be?
- 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
The maintenance of a functional corpus luteum to produce progesterone for..?
- 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)
What is the signal for MRP in Fe & Ca?
none needed
What is the signal for MRP in Ru?
Interferon Tau from trophectoderm
What is the signal for MRP in Sw?
Estradiol (need 2 embryos per horn) from trophectoderm
What is the signal for MRP in Eq?
proteins/ embryo migration
How does IFN tau prevent luteolysis in Ru?
- 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
What are the endocrine physiological mechanisms for IFN Tau?
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
How is conceptus growth dependent on IFN-tau secretion?
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)
How does estradiol re-route PGF2a to prevent luteolysis in the sow?
- 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
What are the other roles of estradiol in sow?
- 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
What is PGE2?
- 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))
What is the importance of the Eq conceptus?
- 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
Why does trans-uterine migration of the Eq conceptus occur?
- 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
What is attachment or implantation?
movement & transient attachment, followed by firm adhesion, of trophectoderm to uterine lumenal & superficial glandular epithelia
What are the phases of attachment/implantation?
- 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
What is uterine receptivity?
- 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
