A Novel Group of Interferons Associated with the Early Ovine and Bovine Embryo

Abstract

Recently, two proteins, ovine trophoblast protein-1 (oTP-1) and bovine trophoblast protein-1 (bTP-1), that are major products of the preimplantation ovine and bovine embryo, respectively, have been shown to be interferons (IFNs). Both proteins belong to an IFN-a subfamily whose polypeptide chains are 172 amino acids long. oTP-1 and bTP-1 have been strongly implicated in triggering maternal responses to the presence of a viable embryo and in maintaining pregnancy. Thus, a new and totally unsuspected role for a specific kind of IFN-a in the reproductive physiology of sheep, cattle, and possibly other species of mammal has become evident. Maternal recognition of pregnancyIn most mammals the lifespan of the corpus luteum of the ovary must be extended during pregnancy so that progesterone production will be continued. This steroid acts on the uterine lining, known as the endometrium, to maintain a milieu appropriate for the developing conceptus (the embryo plus its surrounding membranes). Therefore, the prevention of luteal regression is crucial and depends upon a chemical signal or signals that originate from the conceptus. This phenomenon, described as "maternal recognition of pregnancy," is one of a series of coordinated interactions that occurs between the conceptus and the mother as pregnancy proceeds.Hysterectomy (removal of the uterus) in ewes and cows and many other species, but not in primates, extends the lifespan of the corpus luteum for a period almost equivalent to the length of gestation.1" This persistence of the corpus luteum following hysterectomy indicates that the uterus is the source of the substance that causes luteal regression. Evidence has accumulated that the release of PGF2a by the uterus in the late luteal phase of the estrous cycle is the mechanism responsible for the destruction of the corpora lutea in domestic farm animals.'" In ewes, for example, the uterine endometrium begins to produce PGF2a on days 13 and 14 of the 17-day estrous cycle. At about that time, progesterone levels begin to fall and the animal returns to estrus (heat). In pregnancy, by contrast, the release of PGF2a is attenuated, and the corpus luteum continues to function.Until recently the nature of the conceptus products(s) involved in the rescue of the corpus luteum remained obscure. It was known from embryo transfer experiments that the product must first be produced around days 12-13 because transfers to nonpregnant ewes up to that time frequently succeeded, and removal of embryos from pregnant ewes after that time delayed a return to estrus.1231 373 ROBERTS In addition, homogenates from day 14-15 conceptuses infused into the uterus could extend luteal function in nonpregnant ewes.'4' The active ingredient was sensitive to heat and protease treatment and was not produced by conceptuses much older than 21 days of age.'45' oTP-1In 1982 a protein was identified that was secreted into the medium when sheep conceptuses were cultured in vitro.|6' The synthesis of this protein appeared limited to the critical day 13-21 peri...

Production of two species of interferon by Large White and Meishan pig conceptuses during the peri-attachment period

“…The levels of activity in the present study were higher than reported by Cross & Roberts (1989 (Cross & Roberts, 1989 (Roberts, 1989), pig interferon activity seems to appear and to peak on about the same days. In sheep, oTP-1 synthesis followed by quantifying specific mRNA from conceptuses in culture (Farin et ai, 1989) (Geisert et ai, 1982b).…”

No Detection of Interferon‐γ Activity During Early Pregnancy in the Mouse

“…lA). The aspect 24-h postinfection revealed two main characteristics: (1) a complete collapse of blastocysts, except those that were not hatched; and (2) a gross damage of L 929 cells as shown by the appearance of giant cells corresponding to syncitia. The as- (Table I).…”

“…In several animal species, interferons (lFNs) are found to be secreted by the embryonic trophoblast at the time of implantation. 1 In ruminants, embryonic IFNs related to type I IFN, identical to the known trophoblast protein-l (TP I) or trophoblastins, playa role in the maternal recognition of pregnancy, by maintaining the corpus luteum (CL) functions. [2][3][4] Recent results indicate that equine embryos might also secrete TPI-like IFN.…”

Interferons as Hormones of Pregnancy*

“…Several reviews have been published on various aspects of this topic (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). This discovery attracted considerable attention because it revealed a new and completely unsuspected role for a cytokine as a reproductive hormone.…”