Immunocytochemical localization of estrogen and progestin receptors in the baboon (Papio anubis) uterus during implantation and pregnancy

Abstract

Although estrogen and progesterone are essential for the establishment of pregnancy in primates, localization of their specific receptors in uterine cell types during pregnancy has not been investigated. Therefore, uteri were obtained from baboons during the menstrual cycle, after steroid treatment, or during early pregnancy on days 18, 25 and 32 postovulation. Uterine and placental tissues were also collected from baboons during late pregnancy. Tissues were processed for indirect immunocytochemical localization with specific monoclonal antibodies against estrogen receptor (ER; H222) and progestin receptor (PR; JZB39). Identification of specific cell types was confirmed by iron-hematoxylin/van Gieson and Gimori's stains. Specific staining for steroid receptors was detected only in the nucleus. In the absence of ovarian steroid hormones (ovariectomized baboons), ER were present in glandular epithelium, stroma, and myometrial smooth muscle cells (SMC). In contrast, PR were absent from all uterine cell types. In the estrogen-dominated (follicular and estradiol treatment) uterus, ER and PR were detected in the nuclei of glandular and surface epithelium, stroma, and myometrial SMC. Elevated progesterone levels (luteal or after progesterone treatment) resulted in a loss of nuclear ER in stroma and epithelium, except in the deep glandular epithelium in the basalis. PR was maintained in the stroma throughout the endometrium, but was detected only in the epithelium of the deep glands. The myometrial SMC contained both ER and PR. In early pregnancy, ER was absent from the glands and stroma as early as day 18 postovulation, but was present in the wall of spiral arteries, blood vessels, and myometrial SMC. On day 18 postovulation, staining for PR was absent from all glandular epithelium, but was maintained in the stroma surrounding the glands and spiral arteries, the wall of spiral arteries, blood vessels, and myometrial SMC. Stroma away from glandular epithelium contained few PR-positive cells. This staining pattern persisted throughout early pregnancy. No apparent differences in ER and PR localization were evident between the implantation and nonimplantation sites of the endometrium and myometrium. In late pregnancy, ER were only present in the SMC of the myometrium; however, PR were detected in stroma and myometrial SMC. The maternally derived decidua expressed PR, but not ER, in the majority of cells. In contrast, fetally derived tissues, placenta, and amnio-chorion, did not contain either ER or PR at any stage of pregnancy. Clearly, ER and PR persist in particular uterine cell compartments despite the continual high levels of progesterone in pregnancy and, thus, support a receptor-mediated mechanism for estrogen and progesterone regulation of implantation and pregnancy.