UTERINE PREPARATION FOR IMPLANTATION IN THE MOUSE IS ASSOCIATED WITH COORDINATE EXPRESSION OF ESTROGEN-RESPONSIVE FINGER PROTEIN AND ESTROGEN-RECEPTOR

Estrogen-responsive finger protein (Efp) is a member of the RING finge r-containing proteins. It is a putative transcription regulator that i s speculated to amplify estrogen actions in the target organs. The pre sent study examined the temporal and cell-type specific expression of Efp mRNA in the periimplantation mouse uterus (days 1-8) by Northern a nd in situ hybridization. Consistent with previous observation, a 6.0- kb transcript was detected in uterine RNA samples. The steady-state le vels of Efp mRNA in whole uterine RNAs exhibited modest fluctuations d uring the periimplantation period. However, results of in situ hybridi zation showed cell-specific distribution of Efp mRNA in the periimplan tation uterus in a temporal manner. On days 1-2 of pregnancy, distinct autoradiographic signals for Efp mRNA were detected in uterine lumina l 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 inte nsity was higher in stromal cells immediately surrounding the implanta tion chamber, However, on days 6-8, Efp mRNA was localized throughout the deciduum. To determine whether ovarian steroids influence the uter ine expression of this gene, cell-specific localization of Efp mRNA wa s examined in the adult ovariectomized mouse uterus at 12 hr and 24 hr after an injection of estradiol-17 beta (E(2)) or progesterone (P-4). An injection of E(2) caused a modest increase in Efp mRNA levels in t he luminal and glandular epithelia, while stromal cell accumulation oc curred after an injection of P-4. These results suggest that Efp is in volved in P-4/E(2)-mediated uterine cellular proliferation and/or diff erentiation. Since previous studies showed that Efp is colocalized wit h estrogen receptor (ER) in target cells, we also examined the cell-sp ecific nuclear localization of ER in the periimplantation mouse uterus by immunohistochemistry. On days 1-2 of pregnancy, nuclear staining w as distinct in the luminal epithelium and glandular epithelium. In con trast, nuclear staining was noted in stromal cells on days 3-4. Howeve r, glandular epithelium showed distinct staining during this period. O n day 5, stromal cells surrounding the lumen at the mesometrial site w ere ER-positive, On days 6-8, the intensity of nuclear staining was ve ry low, and limited to the cells adjacent to the luminal epithelium. T he coordinate expression of Efp and ER in specific uterine cells durin g the preimplantation period (days 1-4) was consistent with the absolu te requirement for estrogen in the preparation of the uterus for impla ntation, Since the amount of estrogen required for the preparation of the uterus is minuscule as compared to that of P-4, these results sugg est that the coexpression of Efp with ER is involved in amplifying the estrogen effects required for uterine cell proliferation and/or diffe rentiation during implantation, In contrast, discoordinate expression of Efp and ER during the postimplantation period (days 5-8) suggests p rimary dependence of the decidualization process on P-4, but not estro gen. (C) 1997 Wiley-Liss, Inc.