Uterine preparation for implantation in the mouse is associated with coordinate expression of estrogen-responsive finger protein and estrogen receptor.

Abstract

Estrogen-responsive finger protein (Efp) is a member of the RING finger-containing proteins. It is a putative transcription regulator that is speculated to amplify estrogen actions in the target organs. The present study examined the temporal and cell-type specific expression of Efp mRNA in the periimplantation mouse uterus (days 1-8) by Northern and in situ hybridization. Consistent with previous observation, a 6.0-kb transcript was detected in uterine RNA samples. The steady-state levels of Efp mRNA in whole uterine RNAs exhibited modest fluctuations during the periimplantation period. However, results of in situ hybridization showed cell-specific distribution of Efp mRNA in the periimplantation uterus in a temporal manner. On days 1-2 of pregnancy, distinct autoradiographic signals for Efp mRNA were detected in uterine luminal and glandular epithelia. However, on days 3 and 4, the accumulation of Efp mRNA occurred in stromal cells, in addition to its presence in the epithelium. After initiation of implantation on day 5, signal intensity was higher in stromal cells immediately surrounding the implantation chamber. However, on days 6-8, Efp mRNA was localized throughout the deciduum. To determine whether ovarian steroids influence the uterine expression of this gene, cell-specific localization of Efp mRNA was examined in the adult ovariectomized mouse uterus at 12 hr and 24 hr after an injection of estradiol-17 beta (E2) or progesterone (P4). An injection of E2 caused a modest increase in Efp mRNA levels in the luminal and glandular epithelia, while stromal cell accumulation occurred after an injection of P4. These results suggest that Efp is involved in P4/E2-mediated uterine cellular proliferation and/or differentiation. Since previous studies showed that Efp is colocalized with estrogen receptor (ER) in target cells, we also examined the cell-specific nuclear localization of ER in the periimplantation mouse uterus by immunohistochemistry. On days 1-2 of pregnancy, nuclear staining was distinct in the luminal epithelium and glandular epithelium. In contrast, nuclear staining was noted in stromal cells on days 3-4. However, glandular epithelium showed distinct staining during this period. On day 5, stromal cells surrounding the lumen at the mesometrial site were ER-positive. On days 6-8, the intensity of nuclear staining was very low, and limited to the cells adjacent to the luminal epithelium. The coordinate expression of Efp and ER in specific uterine cells during the preimplantation period (days 1-4) was consistent with the absolute requirement for estrogen in the preparation of the uterus for implantation. Since the amount of estrogen required for the preparation of the uterus is minuscule as compared to that of P4, these results suggest that the coexpression of Efp with ER is involved in amplifying the estrogen effects required for uterine cell proliferation and/or differentiation during implantation. In contrast, discoordinate expression of Efp and ER during the postimplantation period (days 5-8) suggests primary dependence of the decidualization process on P4, but not estrogen.