Differential uterine expression of estrogen and progesterone receptors correlates with uterine preparation for implantation and decidualization in the mouse

The present investigation examined the spatiotemporal expression of estroge n receptors (ER-alpha and ER-beta) and progesterone receptor (PR) in the pe riimplantation mouse uterus (days 1-8). ER-alpha messenger RNA (mRNA) was d etected at much higher levels in the periimplantation uterus compared with that of ER-beta mRNA, the levels of which were very low in all uterine cell s during this period. Results of in situ hybridization demonstrated express ion of ER-alpha mRNA primarily in the luminal and glandular epithelia on da ys 1 and 2 of pregnancy. On days 3 and 4, the accumulation was localized pr imarily in stromal cells in addition to its presence in the epithelium. Fol lowing implantation on day 5, the accumulation of this mRNA was more conden sed in the luminal and glandular epithelia, but declined in the subluminal epithelial stroma at the sites of implanting embryos. On days 6-8, the accu mulation of ER-alpha mRNA was primarily localized in the secondary decidual zone (SDZ) with more intense localization in the subepithelial cells at th e mesometrial pole. In contrast, signals were very low to undetectable in t he primary decidual zone (PDZ), and no signals were detected in implanting embryos. The undifferentiated stroma underneath the myometrium also showed positive signals. The immunolocalization of ER-alpha protein correlated wit h the mRNA localization. Western blot analysis showed down-regulation of ER -alpha in day 8 decidual cell extracts consistent with the down-regulation of ER-alpha mRNA in decidual cells immediately surrounding the embryo on th is day. The expression pattern of PR was also dynamic in the periimplantati on uterus. On day 1, the accumulation of PR mRNA was very low to undetectab le, whereas only a modest level of accumulation in the epithelium was noted on day 2. On days 3 and 4, the accumulation of this mRNA was detected in b oth the epithelium and stroma. In contrast, the expression was restricted o nly to the stroma with increased signals at the sites of implantation on da y 5. On days 6-8, PR mRNA accumulation increased dramatically throughout th e deciduum. The localization of immunoreactive PR correlated with the mRNA distribution in the periimplantation uterus. Taken together, the results de monstrate that the expression of ER-alpha, ER-beta, and PR is differentiall y regulated in the periimplantation mouse uterus. This compartmentalized ex pression of ER and PR provides information regarding the sites of coordinat ed effects of estrogen and progesterone in the preparation of the uterus fo r implantation and decidualization during early pregnancy.