Recent developments and potentialities for reducing embryo mortality in ruminants: the role of IFN-t and other cytokines in early pregnancy

Abstract

This review considers the potential reduction of embryo mortality in vitro and in vivo in ruminants. Data on cytokines provided by different fields of reproductive immunology and biology were collated. Because of the crucial importance of the local interactions between the embryo and its dam, the expression of growth-factor and cytokine genes was analysed in the embryo proper, trophoblast, oviduct and endometrium by reverse transcriptase polymerase chain reaction in sheep and in cattle during the pre- and periimplantation periods. Many deleterious cytokines, such as tumour necrosis factor-α, intereron-γ (IFN-γ ), interleukin-2 (IL-2), and beneficial cytokines, such as transforming growth factor-β, leukaemia inhibiting factor, colony-stimulating factor-1 (CSF-1), ganulocyte–macrophage CSF, IL-1, IL-3, IL-4, IL-6, IL-10 and IFN-γ appeared to be involved in embryo survival in ruminants and other species. Their administration is efficient in a murine experimental model (CBA/J DBA/2) of embryonic and fetal mortality. For instance, recombinant ovine IFN-&tgr; (roIFN-&tgr; ) injected at the moment of implantation drastically reduces embryonic mortality in this model. In ruminants, roIFN-&tgr; and recombinant bovine IFN-&tgr; are very efficient in maintaining progesterone luteal secretion in cyclic animals. The involvement of IFN-&tgr; in the mechanisms of maternal pregnancy recognition are particularly detailed in relation to inbition of 13,14 dihydro-15-keto-prostaglandin F_2α (PGFM) pulses and oxytocin uterine receptivity. A synthetic model of the anti-luteolytic effects of IFN-&tgr; on the endometrial cell is proposed. Finally, the particular potential of serum pregnancy-specific proteins (PSPs: PSPB, PSP60, pregnancy-associated glycoprotein) for monitoring embryo survival, with examples given for cattle and sheep is underlined.