Transcript INTERFERON TAU-ROLE IN EMBRYO IMPLANTATION

INTERFERON TAU-ROLE IN
EMBRYO IMPLANTATION
Paras Yadav*, Jaspreet Singh Arora*, Sachinandan De*, Tirtha Kumar
Datta*, Surender Lal Goswami*, Aarti Bhardwaj$, Shalini Jain# and Hariom
Yadav#
*Animal Biotechnology, #Animal Biochemistry Division, National Dairy Research Institute,
Karnal-132001, Haryana, India
$Meerut
Institute of Engeenering and Technology, Meerut, U.P., India
EMBRYO MORTALITY
30-40% of fertilization are lost due to embryo demise.
Nearly 65% of all embryonic loss occurs between days
6-18 days of pregnancy
Factors affecting Embryonic death
genotypic factors
Nutritional effects
Effects of energy and protein
Conceptus signal
Role of progesterone
Infectious agents
other possible factors, age breed and affect of male
Spencer et al., 2004
Spencer et al., 2004
Spencer et al.,2004
Implantation Window
Implantation of the conceptus in domestic farm species
Interferon tau
• Interferon tau 172 a.acid protein secreted
by the trophectoderm of the conceptus
( Bazer et al.,1991)
• Gives the first pregnancy signal (Roberts
et al.,1999)
• Prevents development of the endometrial
luteolytic mechanism (Spencer and
Bazer,2002)
Mechanism of action
Interferon tau suppress estrogen receptor and oxytocin
(OTR) expression at transcription level
Oxytocin induces uterine release of luteolytic
prostaglandin F2alpha pulses
Prostaglandin F2alpha result in structural and functional
regression of the ovarian CL
( Fleming et al.,2001 )
Hypothetical model of IFN-tau stimulated gene activation and effects
on molecules involved in the PGF2a synthetic pathway
(A) Relative changes in circulating hormone levels and ovarian changes
(B) Changes in endometrial hormone response during the estrous cycle
(A) Relative changes in circulating hormone levels during early pregnancy
(B) Changes in endometrial hormone response during early pregnancy
Transcription of the ER and OTR
genes are lower in pregnant
and IFN treated endometrium
( T.H.E.Spencer et al.,1996 )
Variants of interferon tau gene
• Multiple gene encodes for IFN-Tau
• Genes are not expressed equivalently
• Variants shows considerable differences in biological
activity
(Alan D Eley,1998)
Differences in amounts of mRNA for variants of ovlFN-r relative
to actin mRNA during conceptus development.
(Alan D Eley,1998)
In Vitro secretion of IFN-Tau bovine
• Cultured with TCM 199 shows less
secretion of IFN
• Cultured with B2 &BRL shows high IFN
secretion
• Hatched blastocysts shows high secretion
of IFN than non-hatched ones
(MiodragStojkovic,1995)
( Miodrag Stojkovic,1995 )
Recombinant interferon –tau
• Non glycoslated protein produced in E.coli
• Oestrus cycle synchronized
• Inter-oestrus interval increases up to six
days due to increase in CL life span
( E.C.L.Bleach et al.,1998 )
a)Untreated heifers, b) Heifers treated with rbIFN )