Trophoblastic Interferons: Do they Modulate Uterine Cellular Markers at the Time of Conceptus Attachment in the Pig?

Abstract

Between days 12 and 20 of pregnancy, the trophectoderm of the porcine conceptus secretes two species of interferons (IFN): IFN-γ (Type II), which is produced in substantial amounts, and IFN-δ (type I), for which secretion peaks at days 15–16 of gestation. The role of these embryonic IFNs is not known. We made the assumption that, in the pig, one possible role of these IFNs may be the remodelling and/or depolarization of the uterine endometrial epithelium, as a prerequisite for implantation and establishment of a functional placenta. A comparative analysis by immunohistochemistry of several cell membrane markers and ECM components of the cyclic and pregnant uterus was performed at day 15 post-oestrus. The markers were those likely to differ between a pregnant and cyclic uterus, or between different stages of pregnancy. A highly specific marker of IFN-γ activity, namely MHC class II antigens in the uterine mucosa, was also examined. This study provides so far unreported data: in the endometrial epithelium of the pregnant uterus, we observed a partial relocalization of ZO-1, a marker of epithelial tight junctions, thus suggesting significant changes to the endometrial polarity. Heparan-Sulphate Proteoglycan (HSPG) expression did not differ significantly between cyclic and pregnant uteri. In contrast with the accepted rodent model of trophoblast-uterus adhesion, the porcine trophoblast and luminal epithelium were negative for HSPG. Finally, MHC class II antigens were absent from the cyclic uterus, but markedly induced in the day 15 pregnant uterus, particularly in endothelial cells, suggesting that IFN-γ may indeed cross the maternal epithelium. This hypothesis was supported by the observation of IFN-γ immunoreactivity associated with clusters of endometrial cells in the pregnant uterus.