Maternal recognition of

pregnancy and Implantation

SUBMITTED BY :ANANYA SHARMA

REG. NO: J-21-MV-669
SUBMITTED TO :Dr UTSAV SHARMA
PROF. AND HEAD(VGO)
Maternal recognition of pregnancy
• Maternal recognition of pregnancy (MRP) is a
process by which an early conceptus signals its
presence to the maternal system and prevents
the lysis of the corpus luteum, thus ensuring a
maternal environment supportive of pregnancy
continuation
• This maternal endocrine response is detectable
before the blastocyst is attached to the
endometrium by microvilli
• It includes rescue of CL and maintenance of
pregnancy
Agents of MRP
• MRP in ruminant-
• The agent for MRP in ruminant is IFNτ.
• IFNτ acts on the endometrium in a paracrine manner to
prevent luteolysis, thereby maintaining the CL and
production of progesterone
• IFNτ is a Type I interferon with potential antiviral,
antiproliferative and some immunomodulatory biological
activities
• This implies that apart from being the signal for MRP, IFNτ
plays other roles in early pregnancy in ruminants.
• These include protection of the conceptus or uterus against
viral infection and modulating the maternal immune
response
• The size of the blastocyst is a factor that determines the
amount of IFNs produced
• Mechanism of action of IFNτ

• Oxytocin is responsible for episodic release of PGF2a from the

endometrium and this requires Oxytocin coupling with its receptor
• IFNτ causes inhibition of oestrogen receptor (ER) expression, which in
turn, abolishes Oxytocin receptor expression on the endometrial
luminal epithelia
• IFNτ acts locally in a paracrine manner to suppress the expression of
estrogen receptor on the luminal epithelia and superficial glandular
epithelia
• This in turn delays the Oxytocin receptors coupling on the endometrial
epithelia.
• The consequence is that the endometrium fails to produce the
luteolytic agent PGF2α because of failure of Oxytocin to couple with its
receptor which is essential for PGF2α synthesis
• Therefore, luteolysis does not occur and CL is sustained for continuous
production of progesterone.
• The action of IFNτ is based on alteration in the ratio of
PGE2:PGF2α expression in the endometrium in favour
of PGE2, which unlike PGF2α is known to be
luteotrophic.
• It is believed that the endometrium produces PGF2α
even during pregnancy but at a very low and
insufficient rate.
• In bovine, IFNτ causes down regulation of Oxytocin
receptor as well as cyclooxygenase 2 (COX-2)
expression and hence, reduced expression of PGF
synthase because COX-2 is a rate limiting enzyme that
determines the synthesis of PGF synthase, while the
PGF synthase is responsible for the synthesis of PGF2α.
• The final outcome is reduced expression of PGF2.
IFNτ from trophoectoderm
causes down regulation of
ER and OTR

Progesterone produced by
CL activates
progestomedins (growth
factor)

Progestomedins act via their

Histotroph serves as
receptors in paracrine fashion
nutritional source for early
on uterine epithelium to
embryo
stimulate histotroph secretion
• In the sow:

• The conceptus of the pig produces estradiol between d 11

and 12 after ovulation (coincides with the elongation of the
conceptus)
• Estradiol serves as the signal for maternal recognition of
pregnancy
• - PGF2α is produced by the endometrium re-routed into
the uterine lumen and metabolized, rather than being
drained by the uterine veins -> luminal PGF2α has little
access to the circulation and can’t cause luteolysis
• The sow must have at least two conceptuses in each
uterine horn for pregnancy to be maintained
• MRP in mare Trans uterine migration of equine conceptus

• Both conceptus and endometrium

synthesise PGE2 during early
pregnancy
• PGE2 by antagonising the luteolytic
effect of PGF2a causes MRP
• The presence of the conceptus helps
to prevent Luteolysis
• The conceptus must migrate within
the uterus between 12 to 14 times per
day during days 12, 13, and 14 of
pregnancy in order to inhibit PGF2α
production.
• 1) This migration appears to be very
important because the early embryo
does not elongate
• 2) Conceptus must “touch” enough
receptors or secrete “proteins” and
place near(on) receptors to maintain
pregnancy
• MRP in dogs and cats
• MRP is not required for sustainance of pregnancy
in these species.
• Whether is a conceptive or nonconceptive, CL is
retained for the same period of time (about 60
days).
• This culminates into exhibition of pseudo-
pregnancy
 Molecules involved in
Spp
MRP
Ruminants INF-τ

Mare Reduced COX-2, embryo mobility,

endometrial prostaglandins
synthesis inhibitors, uterocalins
Sow Conceptus derived estrogen that
sequesterates the PG into lumen
where it is inactivated
 Implantation
• The process in which the blastocyst physically
and physiologically comes into intimate
contact with uterus is called implantation
•Bruce effect or
pregnancy block- It is
the tendency of female rodent
to terminate their pregnancy
before implantation following
exposure to scent of an
unfamiliar male
 Types of Implantation

Interstitial Ecentric Centric

Found in Humans Found in rats Found in domestic

Embryo enters the Luminal epithelium forms an animals
uterine wall invagination to surround the Embryo remains in
trophoblast uterine lumen
 Mechanism of Implantation
• The apical surface of the uterine epithelium is initially
covered by a thick glycocalyx that diminishes as the
time for conceptus attachment approaches.
• Transmembrane glycoprotein, termed Muc1,is
abundant during the non receptive phase of pregnancy
and could serve as an anti adhesion factor .
• The presence of Muc-l is greatly reduced, if not absent
, during the period of conceptus attachment to the
uterine surface
• Timing of implantation is regulated by length of time
for which the uterine endometrium is exposed to
progesterone stimulation
• Serum concentrations of progesterone rapidly rise following
formation of the corpus luteum .
• Over an 8 to 10 day exposure to progesterone, progesterone
receptors in the uterine epithelium down-regulate leading to a
loss of the direct effect of progesterone on this cell type.
• Since epithelial synthesis of Muc-l is stimulated by progesterone,
loss of progesterone receptor from the uterine epithelium would
reduce Muc-I production and open a receptive state for
conceptus attachment
• Rodents and primates have blastocysts that penetrate into the uterine
mucosa by phagocytizing and digesting through the uterine luminal
epithelium as they migrate into the uterine stroma.
• These embryos are thus encapsulated beneath the uterine luminal
surface.
• Transformation and proliferation of the uterine stromal cells (referred to
as decidualization) accompany this invasive process in the vicinity of the
developing blastocyst.
• The implantation in the mouse and rat is triggered by estrogen release
from ovarian follicles on day 4 of pregnancy.
• Implantation in large domestic farm species is superficial and noninvasive
and involves phases of trophoblast-uterine epithelial cell apposition and
adhesion .
• The porcine trophoblast, however, does exhibit invasive properties when
placed in an ectopic site, such as the kidney capsule.
• This invasive property results from conceptus production of proteolytic
enzymes such as plasminogen activator and other proteases.
• Porcine conceptuses begin to attach to uterine surface on day 13, with
attachment completed across the trophoblastic surface between days 18
to 24
• Attachment is through interdigitation of uterine and
trophoblastic microvilli covering the complete interface
between the two layers, except where the trophoblast
overlies the openings of uterine glands
• The trophoblastic surface in these areas becomes modified to
form specialized absorptive structures, called areolae , that
allow nutrient uptake by the developing conceptus.
• Loss of Muc-I allows adhesion between the trophoblast and uterine
epithelium
• Removal of the large glycoprotein in may permit interaction between
adhesive factors such as the integrins and their receptors
• Conceptus attachment in ruminant species involves both
caruncular and intercaruncular areas of the uterine
endometrium.
• A transitory attachment first occurs as the bovine and ovine
conceptus develop finger-like villi (papillae) that project into the
lumen of the uterine glands.
• These papillae provide a temporary anchor and absorptive
structure for the conceptus as more complete attachment
progresses.
• Loss or reduction in the height of trophoblastic surface
microvilli permits close surface contact with the uterine
epithelial microvilli.
• The uterine epithelium presses into
the trophoblastic surface; interlocking
with the cytoplasmic projections on
the trophoblast surface until the
trophoblast microvilli redevelop,
forming a more complex attachment.
•Placental attachment in ruminants is
characterized by the appearance of
binucleate cells arising from
uninucleate cells of the trophoblast.
• Binucleate cells first appear on day 17
and are present throughout gestation

➢These cells migrate and fuse with the underlying uterine surface
epithelium to form multinucleate cells or a syncytium.
➢The syncytium may be involved in immunologic protection of the
conceptus and the transfer of placental lactogen synthesized by the
binucleate cells into the maternal vascularcirculation
Down
regulation of
muc-1 gene at
time of ZP
shedding
THANK
YOU