Estrogen and progesterone play an important role in the development and implantation of preimplantation embryos. However, it is controversial whether these hormones act directly on the embryos. The effects of these hormones depend on the existence of their specific receptors. To determine whether estrogen receptor (ER) There are no reports of natural mutations that result in either deficient estrogen synthesis or resistance to estrogen action. This contrasts with testosterone synthesis and action, where single-gene mutations that interfere with both processes have been characterized in many species. This difference has led George and Wilson (1) to suggest that such estrogen-related mutations may be lethal at an early stage of development.Estrogen and progesterone play key roles in the establishment and maintenance of pregnancy. Elimination of these hormones from pregnant animals causes deleterious effects on the development and implantation of the embryos. Hypophysectomy of pregnant rats was shown to result in the delayed entry of eggs into the uterus, expulsion of eggs from the uterus, and retarded development of eggs. Injection of estrone and progesterone significantly reversed this effect (2). Delayed implantation has been observed in ovariectomized mice treated with progesterone only (3). Dormant blastocysts can be reactivated by the injection of estrogen (4, 5). Estrogen and progesterone stimulate the metabolism of delayed implantation mouse embryos (6). It appears to be important to maintain the concentrations of estrogen and progesterone at appropriate levels relative to each other. Elevated ratios of estradiol to progesterone were shown to inhibit blastocyst metabolism and implantation (7). Since these experiments were performed on ovariectomized animals receiving exogenous hormones, it is not clear whether the hormones acted directly on the embryo or indirectly through the mother's reproductive tract. Some authors claimed that the effects were indirect, since retardation ofThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. embryo development and inhibition of implantation were observed when embryos were grown in oviductal fluid obtained from estrogen-treated, ovariectomized mice, whereas no such effects were observed when embryos were grown in defined medium with estrogen (8). In contrast, studies by Smith (9) showed that embryos treated with estrogen in vitro had significantly higher implantation rates when transferred to foster mothers receiving only progesterone, suggesting that estrogen acts directly on the embryo. To obtain an environment without the complication of maternal effects, some investigators turned to in vitro culturing of embryos. Under these conditions, estrogen was shown to affect the uptake and incorporation of nucleic acid precursors (10, 11) and amino acids (12) by mouse blastocysts. It was also shown that antiestro...

We previously showed that estrogen receptor (ER) mRNA is present in preimplantation mouse embryos. The apparent synthesis of ER mRNA by the blastocyst at the time of implantation when estrogen is required was of special interest. A demonstration of the presence of ER protein would support the idea that estrogen can act directly on the embryo.The mouse embryo at the blastocyst stage is differentiated into two cell types, the trophectoderm and the inner cell mass. To determine whether ER mRNA is translated into ER protein and its cell-specific distribution, immunocytochemical analyses were performed in mouse blastocysts. ER

In normal estrogen target tissues, estrogen action is mediated through a specific nuclear transcription factor, the estrogen receptor (ER). The site of estrogen action in the developing organism is therefore determined by cells that contain ER and other necessary tissue and gene-specific components for estrogen-mediated transcription. Immunocytochemical methods were used to determine the cellular localization and tissue distribution of ERs in reproductive tracts of mouse fetuses. Nuclear staining for ER was observed in reproductive tracts at fetal days 13 to 15. ERs were present in the precursors of both male and female reproductive tracts at these early developmental stages, which may be attributable to their similar embryonic origins. However, as the tissues undergo sexual differentiation at later fetal and early neonatal ages, ER increases in the female reproductive tracts as compared with the male. ER was detected by immunoblotting on fetal day 10 (before sexual differentiation) in extracts of whole mouse embryos. To determine whether ER and progesterone receptor genes are expressed earlier in development, we examined RNA from preimplantation mouse embryos using reverse transcriptase-polymerase chain reaction techniques. ER mRNA was found in oocytes and fertilized eggs. Message concentration declined at the 2-cell stage and reached its lowest level at the 5-to 8-cell stage. ER mRNA was not detectable at the morula stage but reappeared at the blastocyst stage. Progesterone receptor mRNA was not detectable until the blastocyst stage. The embryonic expression of ER and progesterone receptor genes in the blastocyst suggests a possible functional requirement for estrogen and progesterone receptors in preimplantation embryos. -Environ Health Perspect 1 03(Suppl 7):69-72 (1995)

In normal estrogen target tissues, estrogen action is mediated through a specific nuclear transcription factor, the estrogen receptor (ER). The site of estrogen action in the developing organism is therefore determined by cells that contain ER and other necessary tissue and gene-specific components for estrogen-mediated transcription. Immunocytochemical methods were used to determine the cellular localization and tissue distribution of ERs in reproductive tracts of mouse fetuses. Nuclear staining for ER was observed in reproductive tracts at fetal days 13 to 15. ERs were present in the precursors of both male and female reproductive tracts at these early developmental stages, which may be attributable to their similar embryonic origins. However, as the tissues undergo sexual differentiation at later fetal and early neonatal ages, ER increases in the female reproductive tracts as compared with the male. ER was detected by immunoblotting on fetal day 10 (before sexual differentiation) in extracts of whole mouse embryos. To determine whether ER and progesterone receptor genes are expressed earlier in development, we examined RNA from preimplantation mouse embryos using reverse transcriptase-polymerase chain reaction techniques. ER mRNA was found in oocytes and fertilized eggs. Message concentration declined at the 2-cell stage and reached its lowest level at the 5- to 8-cell stage. ER mRNA was not detectable at the morula stage but reappeared at the blastocyst stage. Progesterone receptor mRNA was not detectable until the blastocyst stage. The embryonic expression of ER and progesterone receptor genes in the blastocyst suggests a possible functional requirement for estrogen and progesterone receptors in preimplantation embryos.