Intrauterine injection of ovine interferon-tau alters oestrogen receptor and oxytocin receptor expression in the endometrium of cyclic ewes

Abstract

This study determined the effects of intrauterine injections of recombinant ovine interferon-tau; (roIFN-tau; 2 x 10(7) antiviral units/day) or control proteins (6 mg/day) from day 11 to day 14 post-oestrus = day 0) on endometrial expression of receptors fro oestrogen, progesterone and oxytocin in cyclic ewes. Plasma concentrations of progesterone were greater on day 15 in ewes receiving roIFN-tau compared with control proteins (P < 0.02, treatment x day). Ewes injected with roIFN-tau had lower endometrial levels or oestrogen receptor mRNA (P > 0.10) and protein (P < 0.01) on day 15 compared with ewes receiving control proteins. In situ hybridization analysis indicated that oestrogen receptor mRNA was more abundant in the luminal and glandular epithelium of control ewes compared with roIFN-tau-treated ewes. Immunoreactive oestrogen receptor was also present in the luminal and glandular epithelium of control, but not roIFN-tau-treated ewes. Endometrial levels of progesterone receptor mRNA and protein were not different (P > 0.10) between control and roIFN-tau-treated ewes. In situ hybridization analyses indicated that progesterone receptor mRNA abundance was low in endometrial epithelium and stroma of both control and roIFN-tau-injected ewes. Immunoreactive progesterone receptors were present in the endometrial stroma and epithelium of control ewes, but confined to the stroma of roIFN-tau-treated ewes. Oxytocin receptor density was lower (P < 0.01) in the endometrium of ewes injected with roIFN-tau than control proteins; however, oxytocin receptor affinity was not affected (P > 0.10) by treatment. Concentrations of 13,14-dihydro-15-ketoprostaglandin F2a (PGFM) were not increased by exogenous oxytocin administration in control and roIFN-tau-treated ewes on days 10 or 12 post-oestrus. However, on day 14, control ewes responded to oxytocin with increased plasma concentrations of PGFM, whereas ewes receiving roIFN-tau remained unresponsive to oxytocin. These results indicate that the an tiluteolytic effects of IFN-tau are to prevent increases in endometrial oestrogen receptor MRNA and protein and oxytocin receptor density which abrogates uterine release of prostaglandin F2a during maternal recognition of pregnancy. IFN-tau may inhibit the synthesis of oestrogen receptor mRNA by a transcriptional or post-transcriptional regulatory mechanism to suppress oxytocin receptor formation during early pregnancy in ewes.