Localization of c-fos-like proteins in the mouse endometrium during the peri-implantation period

Fos, which collectively refers to protein products of the c-fos proto-oncogene family, was immunohistochemically localized in the mouse uterus to ascertain the effects of steroids on Fos expression in the mouse and to determine the course of Fos expression during normal pregnancy and pseudopregnancy. In ovariectomized mice, Fos was induced in luminal and glandular epithelium and an occasional stromal cell following treatment with 100 ng 17 beta-estradiol (E2). Priming with 2 mg progesterone (P4) for 3 days prior to the administration of 100 ng E2 or giving 100 ng E2 and 2 mg P4 concomitantly induced Fos in the luminal and glandular epithelium with enhanced staining in stromal cells. Priming with P4 before giving E2 had the added effect of inducing Fos at an earlier time point. Progesterone alone failed to induce Fos in any cell type in the uteri of ovariectomized animals. On Days 1 and 2 of pregnancy and pseudopregnancy, Fos was detected in the luminal and glandular epithelium and in the stroma. Staining was decreased by Day 3 and was not detectable by the morning of Day 4. No further staining for Fos was found during subsequent days of pseudopregnancy. On the afternoon of Day 4 of pregnancy, Fos was detected in the epithelium and the antimesometrial stroma. On the morning of Day 5, implantation sites and non-site areas were distinguishable, with Fos present in luminal epithelium and antimesometrial stroma in sites, and in just the luminal epithelium in non-sites. Fos remained in the epithelium of non-sites through Day 7 of pregnancy. In sites on the afternoon of Day 5, staining was found in the luminal epithelium and primary decidual zone. On Day 6, staining was found in the secondary decidual zone, but was absent from the primary zone and epithelium. On Day 7, Fos was also detected in the embryonic trophoblast giant cells and the ectoplacental cone. These results demonstrate that E2 and P4 modulate Fos in the mouse endometrium and that Fos is induced during implantation. Significantly, the embryo appears to induce Fos expression on the afternoon of Day 4, while it is still encased in the zona pellucida.