1. 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

2. 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

3. Spencer et al., 2004

6. Implantation Window Implantation of the conceptus in domestic farm species

7. Interferon tau Interferon tau 172 a.acid protein secreted Interferon tau 172 a.acid protein secreted by the trophectoderm of the conceptus ( Bazer et al.,1991) by the trophectoderm of the conceptus ( Bazer et al.,1991) Gives the first pregnancy signal (Roberts et al.,1999) Gives the first pregnancy signal (Roberts et al.,1999) Prevents development of the endometrial luteolytic mechanism (Spencer and Bazer,2002) Prevents development of the endometrial luteolytic mechanism (Spencer and Bazer,2002)

8. Mechanism of action Interferon tau suppress estrogen receptor and oxytocin (OTR) expression at transcription level Interferon tau suppress estrogen receptor and oxytocin (OTR) expression at transcription level Oxytocin induces uterine release of luteolytic prostaglandin F2alpha pulses Oxytocin induces uterine release of luteolytic prostaglandin F2alpha pulses Prostaglandin F2alpha result in structural and functional regression of the ovarian CL Prostaglandin F2alpha result in structural and functional regression of the ovarian CL ( Fleming et al.,2001 )

9. Hypothetical model of IFN-tau stimulated gene activation and effects on molecules involved in the PGF2a synthetic pathway

10. (A)Relative changes in circulating hormone levels and ovarian changes (B)Changes in endometrial hormone response during the estrous cycle

11. (A)Relative changes in circulating hormone levels during early pregnancy (B)Changes in endometrial hormone response during early pregnancy

12. Transcription of the ER and OTR genes are lower in pregnant and IFN treated endometrium ( T.H.E.Spencer et al.,1996 )

13. Variants of interferon tau gene Multiple gene encodes for IFN-Tau Multiple gene encodes for IFN-Tau Genes are not expressed equivalently Genes are not expressed equivalently Variants shows considerable differences in biological activity Variants shows considerable differences in biological activity (Alan D Eley,1998) (Alan D Eley,1998)

14. (Alan D Eley,1998) Differences in amounts of mRNA for variants of ovlFN-r relative to actin mRNA during conceptus development.

15. In Vitro secretion of IFN-Tau bovine Cultured with TCM 199 shows less secretion of IFN Cultured with TCM 199 shows less secretion of IFN Cultured with B2 &BRL shows high IFN secretion Cultured with B2 &BRL shows high IFN secretion Hatched blastocysts shows high secretion of IFN than non-hatched ones Hatched blastocysts shows high secretion of IFN than non-hatched ones (MiodragStojkovic,1995) (MiodragStojkovic,1995)

17. Recombinant interferon –tau Non glycoslated protein produced in E.coli Non glycoslated protein produced in E.coli Oestrus cycle synchronized Oestrus cycle synchronized Inter-oestrus interval increases up to six days due to increase in CL life span Inter-oestrus interval increases up to six days due to increase in CL life span ( E.C.L.Bleach et al.,1998 ) ( E.C.L.Bleach et al.,1998 )

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