INTERFERON TAU-ROLE IN EMBRYO IMPLANTATION Paras Yadav*, Jaspreet Singh Arora*, Sachinandan De*, Tirtha Kumar Datta*, Surender Lal Goswami*, Aarti Bhardwaj.

INTERFERON TAU-ROLE IN INTERFERON TAU-ROLE IN EMBRYO IMPLANTATIONEMBRYO 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 MORTALITYEMBRYO MORTALITY30-4030-40% of fertilization are lost due to embryo % of fertilization are lost due to embryo demise.demise.Nearly 65% of all embryonic loss occurs Nearly 65% of all embryonic loss occurs between days 6-18 days of pregnancybetween days 6-18 days of pregnancyFactors affecting Embryonic deathFactors affecting Embryonic death genotypic factorsgenotypic factorsNutritional effectsNutritional effectsEffects of energy and proteinEffects of energy and proteinConceptus signalConceptus signalRole of progesteroneRole of progesteroneInfectious agentsInfectious agentsother possible factors, age breed and affect of other possible factors, age breed and affect of malemale

Spencer et al., 2004

Spencer et al., 2004

Spencer et al.,2004

Implantation Window

Implantation of the conceptus in domestic farm species

Interferon tauInterferon tau

• Interferon tau 172 a.acid protein secreted Interferon tau 172 a.acid protein secreted by the trophectoderm of the conceptus by the trophectoderm of the conceptus

( Bazer et al.,1991) ( Bazer et al.,1991)

• Gives the first pregnancy signal (Roberts Gives the first pregnancy signal (Roberts et al.,1999)et al.,1999)

• Prevents development of the endometrial Prevents development of the endometrial luteolytic mechanism (Spencer and luteolytic mechanism (Spencer and Bazer,2002)Bazer,2002)

Mechanism of action Mechanism of action

Interferon tau suppress estrogen receptor and Interferon tau suppress estrogen receptor and oxytocin (OTR) expression at transcription leveloxytocin (OTR) expression at transcription level

Oxytocin induces uterine release of luteolytic Oxytocin induces uterine release of luteolytic prostaglandin F2alpha pulsesprostaglandin F2alpha pulses

Prostaglandin F2alpha result in structural and Prostaglandin F2alpha result in structural and functional regression of the ovarian CLfunctional regression of the ovarian CL

( Fleming et ( Fleming et al.,2001 )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 Transcription of the ER and OTR genes are lower in pregnantgenes are lower in pregnant

and IFN treated endometriumand IFN treated endometrium

( T.H.E.Spencer et al.,1996 )

Variants of interferon tau geneVariants of interferon tau gene

• Multiple gene encodes for IFN-TauMultiple gene encodes for IFN-Tau• Genes are not expressed equivalentlyGenes are not expressed equivalently• Variants shows considerable differences in biological activityVariants shows considerable differences in biological activity

(Alan D Eley,1998) (Alan D Eley,1998)

(Alan D Eley,1998) (Alan D Eley,1998)

Differences in amounts of mRNA for variants of ovlFN-r relativeto actin mRNA during conceptus development.

In Vitro secretion of IFN-Tau bovineIn Vitro secretion of IFN-Tau bovine

• Cultured with TCM 199 shows less Cultured with TCM 199 shows less secretion of IFNsecretion of IFN

• Cultured with B2 &BRL shows high IFN Cultured with B2 &BRL shows high IFN secretionsecretion

• Hatched blastocysts shows high Hatched blastocysts shows high secretion of IFN than non-hatched secretion of IFN than non-hatched onesones

(MiodragStojkovic,1995)(MiodragStojkovic,1995)

( Miodrag Stojkovic,1995 )( Miodrag Stojkovic,1995 )

Recombinant interferon –tauRecombinant interferon –tau• Non glycoslated protein produced in Non glycoslated protein produced in

E.coliE.coli• Oestrus cycle synchronized Oestrus cycle synchronized • Inter-oestrus interval increases up to six Inter-oestrus interval increases up to six

days due to increase in CL life spandays due to increase in CL life span

( E.C.L.Bleach et al.,1998 )( E.C.L.Bleach et al.,1998 )

a)Untreated heifers, b) Heifers treated with rbIFN )