Ontogeny of the estrogen receptor in the human fetal uterus.

Abstract

The role of estrogen and its receptor in the development of the human fetal reproductive tract is unknown, but it may be involved in uterine maturation. In mouse and guinea pig uteri, studies have identified estrogen receptor (ER) protein during the fetal period. In the human, there are no published data regarding the ER during fetal uterine development. The purpose of this study was to investigate the pattern of ER gene and protein expression in the human fetal uterus. Uteri were obtained from abortuses (n = 43; range, 10-24 weeks gestation) of women undergoing elective termination of pregnancy. Reverse transcription-polymerase chain reaction was performed with whole uteri as well as cultured fetal uterine stroma-like cells (n = 15). Immunolocalization studies were performed on frozen uterine sections using the H222 monoclonal antibody (Abbott Laboratories) directed against the ER (n = 20). Western blotting was used to confirm the identity of the ER protein (n = 3). Ligand binding studies were performed using radiolabeled [3H]estradiol (n = 5). Using reverse transcription-polymerase chain reaction, a 263-basepair DNA fragment corresponding to the ER was consistently present in uteri after 15 weeks gestation. By immunohistochemistry, the ER is expressed within the uterine mesenchyme in a discrete cylindrical pattern at the interface of the differentiating endometrial stroma and myometrium. Western blotting confirmed the presence of a protein of an apparent mol wt of 66 kilodaltons, the predicted size of the ER. Ligand binding studies for the ER gave a value less than 8 fmol/mg protein. In summary, the ER gene is expressed in the uterus beginning in the early second trimester during fetal development. ER protein is localized in a discrete cylindrical pattern within the developing uterus. The highly specific location of the ER protein together with the messenger ribonucleic acid data suggest a role for the ER in differentiation of the primitive uterine mesenchyme into stromal and myometrial compartments.