Human fetal testis:: source of estrogen and target of estrogen action

BACKGROUND: Estrogens are involved in masculine fertility and spermatogenesis. However, little is known about estrogen involvement in human testicular organogenesis. Therefore the aim of this study was to investigate the cellular sources and targets of estrogens and their variations in the human testis during fetal development. Expression profiles of aromatase (CYP19) and estrogen receptors (ER) alpha and beta were analysed in human fetal testes at various gestational stages by immunohistochemistry and quantitative RT-PCR. METHODS: Fifty-four archival paraffin-embedded and four frozen fetal testes were studied by immunohistochemistry and real-time PCR. Tissue quality was confirmed by histology and expression of specific functional markers: androgenic enzymes for Leydig cells, anti-Mullerian hormone for Sertoli cells and Steel factor receptor for germ cells. RESULTS: We demonstrate that the human fetal testes express aromatase and ER beta simultaneously in Sertoli, Leydig and germ cells but are devoid of ER alpha. Quantification of positive cells indicates a window of protein expression, especially between 13 and 22-24 weeks. Quantitative RT-PCR confirmed that the human fetal testis expresses CYP19 and ER beta but not ER alpha mRNA. CONCLUSIONS: Our findings suggest that locally produced estrogens influence human testicular development through autocrine and paracrine mechanisms, most notably during the period of maximal testicular susceptibility to endocrine disruptors.