Human fetal testis: Second trimester proliferative and steroidogenic capacities

The period of Leydig cell hyperplasia (14-18 weeks gestation) in human feta l testis is crucial for normal gonad development. We have studied the spati o-temporal distribution of key developmental and functional markers in huma n fetal testis between 13-19 weeks gestation. Proliferating cell nuclear an tigen-positive cells were immunolocalized to both interstitium and tubules. Image analysis confirmed an increase in positive interstitial cells during Leydig cell hyperplasia (P < 0.05). c-Myc was localized to the interstitiu m with no gestational changes. The steroidogenic enzymes 3<beta>-hydroxyste roid dehydrogenase (protein) and cytochrome P450 17 alpha -hydroxylase/C17- 20-lyase (P450c17; messenger ribonucleic acid and protein! were confined to the Leydig cells. The number of immunopositive cells increased between 13 and 19 weeks (P < 0.001). P450c17 mRNA (in situ hybridization) and protein were localized to the same population of interstitial Leydig cells. Androge n receptor and Bcl-2 protein (antiapoptotic) were gradually restricted to t he peritubular myoid cells as gestation progressed. Conversely, Bax protein (pro-apoptotic) was predominantly localized to the tubule Sertoli cells, w hereas the germ cells were Bax immunonegative. In conclusion, human fetal Leydig cell hyperplasia is characterized by incr easing numbers of proliferating cells and increased expression of steroidog enic enzymes. The Bcl-2-positive, Bar-negative status of the peritubular my oid cells may be a strategy for cell survival.