Ovine interferon tau suppresses transcription of the estrogen receptor and oxytocin receptor genes in the ovine endometrium.

Tau interferons (IFNtau) are a unique subclass of the omega interferons that are transiently produced by the trophectoderm of the conceptus (embryo and associated membranes) during early pregnancy in ruminants. IFNtau acts as an antiestrogen on the endometrium to suppress increases in estrogen receptor (ER) and oxytocin receptor (OTR) gene expression which prevents pulsatile production of prostaglandin F2alpha and regression of the corpus luteum or luteolysis. In this study, steady-state levels of ER mRNA and transcription rates of the ER and OTR genes were two-fold lower in the endometrium of pregnant as compared to cyclic ewes on day 15. Levels of ER mRNA and ER and OTR gene transcription were also two-fold lower in the endometrium of day 15 cyclic ewes receiving intrauterine injections of recombinant ovine IFNtau from day 11 to day 14 compared to control ewes. Results suggest that the antiluteolytic action of IFNtau is to suppress transcription of the ER gene by a negative-acting transcriptional mechanism which prevents estrogen-induced increases in OTR gene expression in the endometrium. The novel antiestrogenic effects of IFNtau, combined with its Type I IFN characteristics and low cytotoxicity, suggest that this trophoblast IFN may have potential value as a chemotherapeutic agent for the treatment of infertility, viral disease and estrogen-dependent malignant disorders.