Estrogen inhibits fetal thymocyte development in vitro

Transient involution of the maternal thymus in mice is known to occur during pregnancy. We have previously reported that the hormone responsible for this involution is estrogen. Interestingly, although estrogen crosses the placenta, fetal thymus gland enlarges with advancing gestational age. It is not known if fetal thymocytes are resistant to estrogen or if there are other factors that prevent estrogen from exerting an effect on the development of fetal thymocytes. Therefore we studied the effect of estrogen on isolated fetal thymic glands in vitro. METHOD OR STUDY: Pregnant Balb/c mice were sacrificed at 15 days gestation and fetal thymic lobes were obtained from all fetuses. The glands were cultured in vitro using either control medium or medium to which estrogen was added in two concentrations of 0.5 mg/ 100 ml and 1.0 mg/100 ml. After 12 days of organ culture, total thymocyte counts and phenotypic analysis by three color flow cytometry were performed by using monoclonal antibodies to surface markers of T cells subsets.

Estrogen treatment caused a marked suppression of the total number of fetal thymocytes. All CD4 and CD8 defined T cell subsets were reduced with a disproportionate loss of CD4+ single positive (SP), CD8+ SP: CD4+CD8+ double positive (DP) cells. The early thymocyte developmental stages, based on CD44 and CD25 expression, revealed the CD4-CD8-CD3- triple negative compartment (TN) to be composed of almost entirely the earliest population (CD44+CD25-) with the remaining maturational stages depleted.

This study demonstrates that fetal thymus removed from the intact fetus is susceptible to the inhibitory effects of estrogen. Since the fetal thymus enlarges with advanced gestational age, it is clear that the intact fetus invokes a regulatory mechanism which neutralizes the anti-lymphopoietic action of estrogen observed in the adult female.