Estrogen receptors, estradiol, and diethylstilbestrol in early development: the mouse as a model for the study of estrogen receptors and estrogen sensitivity in embryonic development of male and female reproductive tracts.

To date, there is no conclusive evidence that ERs are present in preimplantation embryos. There are reports that estrogen is made by the rabbit blastocyst (61), and estrogens have been used to induce implantation in mice (62), but whether estrogens act through ERs in the embryo or in the maternal uterus is not known. ERs may be present in early embryos, but if so, levels are below the methods of detection used thus far. Perhaps with more sensitive immunodetection methods, it may be possible to detect ERs in embryos if they are present. Using PCR, messenger RNA for ER has been detected as early as the oocyte stage in mouse embryos (Q. Hou and J. Gorski, unpublished results). This was confirmed recently by Wu et al. (83a). Figure 7 shows a model for the pattern of ER expression in the developing mouse fetus based on the various reports discussed in this review. ERs are present in the 10-day mouse fetus, possibly in the developing ambisexual reproductive tract. Analysis of seven individual 10-day-old fetuses taken from the same litter showed similar levels of an immunostained protein the size of the ER in each fetus (57). The pattern of expression of ER between implantation and the development of the reproductive tract may be the same in male and female mice. Estrogen, acting through ERs, may be one factor (of many) that determines which cells are destined to be part of the indifferent reproductive tract. We were not able to isolate fetal mouse reproductive tracts at an indifferent stage (day 10) due to their very small size. One way to study ER in the indifferent reproductive tract would be to examine these tissues in a larger animal, such as the bovine, using similar immunodetection methods. The distribution of ER in the fetal mouse reproductive tract on fetal days 13 (before sexual differentiation) and 15 (initiation of sexual differentiation) is similar in males and females (71, 72). Thus, estrogen does not appear to be responsible for the initiation of sexual differentiation. Early experiments by Jost (41) showed that removal of the gonad from male or female rabbit fetuses resulted in the female phenotype, which lent weight to the hypothesis that ovarian hormones are not critical in the development of the female phenotype, whereas testicular hormones are essential for the development of the male phenotype.(ABSTRACT TRUNCATED AT 400 WORDS)