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-alpha, interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and beneficial cytokines, such as transforming growth factor-beta, leukaemia inhibiting factor, colony-stimulating factor-1 (CSF-1), granulocyte-macrophage CSF, IL-1, IL-3, IL-4, IL-6, IL-10 and IFN-tau appeared to be involved in embryo survival in ruminants and other species. Their administration is efficient in a murine experimental model (CBA/J x DBA/2) of embryonic and fetal mortality. For instance, recombinant ovine IFN-tau (roIFN-tau) injected at the moment of implantation drastically reduces embryonic mortality in this model. In ruminants, roIFN-tau and recombinant bovine IFN-tau are very efficient in maintaining progesterone luteal secretion in cyclic animals. The involvement of IFN-tau in the mechanisms of maternal pregnancy recognition are particularly detailed in relation to inhibition of 13,14 dihydro-15-keto-prostaglandin F2 alpha (PGFM) pulses and oxytocin uterine receptivity. A synthetic model of the anti-luteolytic effects of IFN-tau 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.

Suppressor of cytokine signalling (SOCS) genes are expressed in the endometrium and regulated by conceptus signals during early pregnancy in the ewe

“…For these SOCS genes, the regulation beyond day 20 of pregnancy cannot result from IFN , whose secretion ends at days 20-21 of pregnancy (Roberts et al 1992, Martal et al 1998. In addition to the persisting endometrial production of cytokines such as LIF, CSF or interleukins 2, 4 or 6 beyond the implantation stage (Martal et al 1997, Rahman et al 2004, ligands and receptors of the ovine placental lactogen (PL)/growth factor (GH) and insulin-like growth factor (IGF) systems are also expressed when the placentation starts. Ovine PL begins to be secreted by the trophectoderm at days 15-16 and ovine GH at day 27.…”

“…Because the crucial functions of SOCS in the regulation of cytokine signalling pathway are well established and numerous cytokines, IFNs, growth factors and hormones are required for a successful implantation (Martal et al 1997), we have hypothesized that the cascade of conceptus and maternal intercellular mediators controlling the endometrium receptivity affects the expression of SOCS genes during the peri-implantation period. The aim of this study was to determine the expression of CIS and SOCSs 1-3 as well as to analyze their regulation by the conceptus signals, especially IFN , in caruncular and intercaruncular endometrium compartments during early pregnancy in the ewe.…”

Interferon-tau, a Type 1 interferon involved in maternal recognition of pregnancy

“…Experiments comparing the potency of an ovine IFN-τ against another sub-type of ovine IFN, however, are not easily performed, but this laboratory has found little difference between an ovine IFN-τ and an ovine IFN-α in their respective abilities to extend estrous cycle length when infused into the uterine lumen of non-pregnant ewes (30). In cattle, limited IFN-α / IFN-τ comparisons have been attempted, but equivalent amounts of protein, rather than comparable quantities of antiviral activity, have been tested (see (31,32). IFN-τ have excellent antiviral activities, at least the equivalent of corresponding IFN-α from the same species (33,34).…”

Effect of the FGF2 SNP11646 on milk production and fertility traits of Holstein cattle

“…Their study has shown that FGF2 is a weak mediator of trophectoderm proliferation but is a strong regulator of IFNT production in bovine trophectoderm cells and blastocyst-stage bovine embryos. IFNT plays a key role in regulating the expression of genes involved in embryo implantation and in protecting the conceptus against maternal rejection (Martal et al 1997), the effect of FGF2 in this context has been proven by Khatib et al (2010).…”