Ovine endogenous betaretroviruses (enJSRVs) and placental morphogenesis

Endogenous retroviruses (ERVs) account for a substantial portion of the genetic pool of every animal species (e.g. approximately 8% of the human genome). Despite their overwhelming abundance in nature, many questions on the basic biology of ERVs are unanswered. The most important question derives from the observations in many animal species, including humans, of abundant ERVs expressed in the female genital tract. Sheep harbor approximately 20 copies of endogenous betaretroviruses (enJSRVs), which are related to an exogenous oncogenic virus, Jaagsiekte sheep retrovirus (JSRV). enJSRVs are abundantly expressed in the ovine placenta and uterine endometrium throughout gestation. Hyaluronidase 2 (HYAL2), which can serve as a cellular receptor for JSRV and enJSRVs envelope (Env), is expressed by the trophoblast giant binucleate cells and multinucleated syncytia of the placenta. Little is known about the cellular and molecular mechanisms that regulate trophoblast differentiation and syncytia formation during synepitheliochorial placentation in sheep. The temporal and spatial alterations in enJSRVs expression in the ovine uterus and placenta support the hypothesis that trophoblast growth and differentiation into binucleate cells and formation of multinucleated syncytiotrophoblast involves enJSRVs Env and possibly their cellular receptor, HYAL2.