11 – Establishment of Pregnancy Flashcards

1
Q

Pregnancy

A
  • Period between fertilization and birth
  • *driven by development of LIVE BIRTH (viviparity) on to mammalian biology
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2
Q

Pregnancy involves main features of

A
  • Internal fertilization (ex. NOT fish)
  • Retention of fertilized egg, embryo, fetus WITHIN female reproductive tract
  • Direct maternal nourishment
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3
Q

Monotremes

A
  • Do NOT have a LIVE birth
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4
Q

Marsupials

A
  • Fetus is born LIVE
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5
Q

Advantages of pregnancy

A
  • Protection from
    o Thermal extremes
    o Osmotic stress
    o Predation
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6
Q

Disadvantages of pregnancy

A
  • Increased maternal energy use
  • Reduced maternal mobility and FECUNDITY
  • Risk of injury (mother and fetus) from immunological and inflammatory responses in utero
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7
Q

Hatching and blastocyst expansion

A
  • Embryos (especially some domestic species) change shape and size
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8
Q

2 groups of mammals in terms of development within uterus and implantation

A
  1. Pre-attachment period within uterus is long (ex. mostly domestic animals)
  2. Blastocyst implants quickly after entering the uterus (ex. primates)
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9
Q

Pre-attachment period within uterus is long (ex. mostly domestic animals)

A
  • Extensive extra-embryonic membrane develop (amnion, allantois and chorion)
  • Maternal recognition of pregnancy signal is produced and signal must occur BEFORE attachment period to uterus
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10
Q

Blastocyst implants quickly after entering the uterus (ex. primates)

A
  • Develop of extra-embryonic membranes occurs AFTER implantation
  • *MRP signal rapidly increased AFTER implantation
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11
Q

Dog (‘attachment’)

A
  • 7-10 days for zygote to reach uterine tubes
  • Intrauterine migration from day 12-17=evenly spaced throughout each horn
  • Fixation and implantation at day 17
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12
Q

Cat (‘attachment’)

A
  • Blastocysts appear to reach uterus by day 6
  • Ellipsoid after that and hatch from zona by day 11
  • Intrauterine migration and begin implantation by day 12
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13
Q

Ruminants and pig: elongation

A
  • Become tubular and then FILAMENTOUS
  • Ex. pigs: by day 12-25 filamentous structure=1m long
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14
Q

Elongation of any conceptus provides

A
  • Maximum surface area of contact between trophectoderm/trophoblast AND maternal uterine epithelium
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15
Q

Ruminant elongated embryo can extend into

A
  • The non-pregnant uterine horn
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16
Q

Horses: elongation

A
  • Do NOT elongate=remains spherical
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17
Q

Histotrophe

A
  • Products from it come from the endometrial glands
  • Nourish embryo during pre-implantation period
    o Survival, development, production of MRP factors, implantation and placentation
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18
Q

What are the secretory products of the endometrial glands?

A
  • Enzymes
  • GFs
  • Cytokines
  • Hormones transported into lumen
  • Transport proteins (ex. for glucose)
  • Nutrients (ex. AA, glucose)
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19
Q

Endometrial glands undergo substantial _____during gestation

A
  • Hyperplasia AND hypertrophy
    o Increase SA for maximum production of histotrophe
  • Ex. ruminants, horse (less in primates)
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20
Q

Luteolysis must be prevented

A
  • In order to establish a pregnancy
    o *don’t want CL to be lost or broken down
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21
Q

Maternal recognition of pregnancy (MRP)

A
  • Dogs and cats: luteal phase is close to duration of actual gestation=no signal required from conceptus
  • Others: luteal phase ends before embryo normally implants=need a signal to prolong a single or number of CL
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22
Q

2 types of recognition signalling from conceptus to maternal system

A
  • Luteotrophic
  • Anti-luteotrophic (PRIMARY one we usually talk about)
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23
Q

Luteotrophic

A
  • A hormone(s) act on CL to maintain luteal function
24
Q

Anti-luteotrophic

A
  • A hormone(s) to prevent uterine release of luteolytic-promoting substances
  • Ex. prostaglandin F2-alpha
25
Q

Signalling from conceptus to maternal system result in maintenance of CL to produce progesterone to:

A
  • Support secretory functions of endometrium, embryonic development, implantation, placentation
  • Negative feedback on hypothalamus and A. pituitary to INHIBIT follicular development (ovulation)
  • Prevention of return to estrus in polyestrous species
26
Q

Day of attachment is ALWAYS going to be

A
  • After the mother has got the recognition signal
  • *if no signal or recognition=attachment will NOT occur
27
Q

What prevents luteolysis in cow, ewe and goat?

A
  • Interferon (IFN) Tau
  • Acts on endometrial cells of uterus and inhibits oxytocin receptor production
    o Oxytocin now WONT stimulate pulsatile PGF2alpha synthesis
  • Increases SECRETION of proteins from endometrial glands
28
Q

Physiological mechanism: paracrine effects on endometrium in ewe and goat

A
  • IFN-tau binds to own receptor and produces an INHIBITORY protein that blocks the estrogen signalling
    o Blocks the production of oxytocin receptor=NO or limited production of PGF2alpha
29
Q

Physiological mechanism: paracrine effects on endometrium in cow

A
  • IFN-tau blocks the oxytocin receptor DIRECTLY
    o NO or limited production of PGF2alpha
30
Q

Physiological mechanism: endocrine (IFN Tau)

A
  • Can be transported from utero-ovarian vein to ovarian artery and then to CL
  • *sustain CL function to produce P4
  • *prevent lytic events of any PGF2alpha on CL
31
Q

IFN Tau can have paracrine effects on endometrium to stimulate

A
  • Conceptus elongation
    o Production of small cytokines
    o Induce expression of genes in endometrium for uterine attachment
    o Stimulate endometrial gland development and function
32
Q

Non-pregnant sow

A
  • Oxytocin from endometrium, P. pituitary and CL promote PGF2alpha production in endometrium=can reach the ovary and initiate luteolysis
33
Q

Pregnant sow

A
  • Estrogen=MPR signal from conceptus
    o Must be secreted between days 11-15
  • Estradiol re-routes PGF2alpha to uterine lumen=destroyed=PREVENTS LUTEOLYSIS
34
Q

Estradiol in sow (from conceptus between day 15-25 of gestation)

A
  • Induces expression of genes in uterus responsible for conceptus attachment
  • Stimulate production of endometrial prolactin receptors
  • *promote uterine gland development and INCREASE ion and nutrient transport from conceptus
  • Promote immune response (TOLERANCE) of progesterone-primed endometrium to implantation
35
Q

Osteopontin (OPN)

A
  • Secreted by uterine luminal epithelium
  • Responsible for endometrial remodelling and conceptus adhesion
  • ‘glue’
36
Q

Estradiol from conceptus stimulates uterine epithelia to secrete

A
  • Prostaglandin E2 (PGE2)
37
Q

PGE2

A
  • Reaches CL from utero-ovarian vein to ovarian artery (like Tau in ruminants)
  • *provides luteoprotective role in CL=maintains CL function
38
Q

MRP signal in equine: unknown

A
  • Day 6.5: trophectoderm of blastocyst begins to secrete a GLYCOPROTEIN containing capsule beneath the ZP
  • Capsule remains until day 22 of pregnancy
39
Q

Importance of equine conceptus

A
  • If remove conceptus at various points=lengthen time required to return to estrus
  • Embryo does produce something that is important
    o Estradiol and estrone (not really involved in CL lifespan)
  • PGF2 alpha is blocked (due to COX2 activity)
  • NO INF secretion
40
Q

During pre-attachment phase in equine

A
  • Horse conceptus is moved over endometrial surface by UTERINE CONTRACTIONS (12-14 times a day)
    o Not elongations
  • Endometrial production of PGF2alpha is significantly REDUCED
41
Q

Migration of horse embryo is critical

A
  • Capsule prevents elongation
  • NEED the movement due to no increase in SA
  • *allows for maternal recognition
42
Q

Attachment or implantation

A
  • Movement and transient attachment followed by FIRM adhesion
    o Trophectoderm to uterine luminal and superficial glandular epithelium
43
Q

Phase 1 of attachment

A
  • Shedding of ZP=hatching
44
Q

Phase 2 of attachment

A
  • Pre-contact period
  • Blastocysts migrate and undergo orientation w/o contact with epithelia
  • Initiate pregnancy recognition signalling
45
Q

Phase 3 of attachment

A
  • Trophectoderm associates with endometrial epithelium for UNSTABLE adhesion
  • Ruminants: microvilli development begins
46
Q

Phase 4 of attachment

A
  • Trophectoderm FIRMLY adheres to luminal epithelium
  • Some: attachment to superficial glandular epithelium
47
Q

Phase 5 of attachment (carnivores, primates and rodents)

A
  • INVASIVE implantation through uterine luminal epithelium into uterine stroma
48
Q

Uterine receptivity represents the

A
  • Interactions between the developmentally competent conceptus and uterine endometrium
49
Q

Uterine receptivity is the

A
  • Restricted period of the uterine cycle
    o Pre-contact
    o Apposition and firm adhesion and invasion
  • *driven by actions of progesterone, estrogens and IFN-tau (ruminants)
  • **loss of mucins from luminal epithelial cells of the endometrium
  • Conceptus has similar receptors and ECM secretion for binding to endometrium
50
Q

Mucins

A
  • Anti-adhesive cell surface glycoproteins
51
Q

Loss of mucins

A
  • ‘unmasks’ surface adhesion molecules on endometrium
  • Selectins
  • Integrins
52
Q

Selectins (surface adhesion molecules on endometrium)

A
  • Low affinity contacts
  • For initial attachment of the conceptus
53
Q

Integrins (surface adhesion molecules on endometrium)

A
  • Higher affinity contacts
  • *AND MATERNAL ECM (osteopontin, fibronectin)=stable adhesion of conceptus
54
Q

Clinical relevance: pregnancy loss

A
  • High rate of pregnancy loss=decreased reproductive performance
55
Q

What are the 2 critical periods that are responsible for majority of pregnancy losses (dairy cattle)

A
  • From fertilization to blastocyst development (10-50%)
  • MRP, conceptus elongation, uterine receptivity (20%)
56
Q

Beef cattle clinical relevance

A
  • fertilization (50%)
  • MRP (16%)
  • after attachment (<6%)
    *4/5 pregnancies are lost without even realizing you were pregnant