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Human Fetal Testis: Second Trimester Proliferative and Steroidogenic Capacities¹

Nutrition and Development, The Rowett Research Institute (T.J.M., R.G.L.), Bucksburn, Aberdeen, Scotland AB21 9SB; and Departments of Obstetrics and Gynecology (T.J.M., P.A.F., D.R.A., R.G.L.) and Medical Genetics (N.H.), University of Aberdeen, Foresterhill, Aberdeen, Scotland AB25 2ZD

Address all correspondence and requests for reprints to: Dr. Richard G. Lea, Division of Maternal-Fetal Biology, The Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen, Scotland AB21 9SB. E-mail: rgl{at}rri.sari.ac.uk

The period of Leydig cell hyperplasia (14–18 weeks gestation) in human fetal testis is crucial for normal gonad development. We have studied the spatio-temporal distribution of key developmental and functional markers in human fetal testis between 13–19 weeks gestation. Proliferating cell nuclear antigen-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 interstitium with no gestational changes. The steroidogenic enzymes 3ß-hydroxysteroid dehydrogenase (protein) and cytochrome P450 17-hydroxylase/C_17–20-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. Androgen receptor and Bcl-2 protein (anti-apoptotic) were gradually restricted to the peritubular myoid cells as gestation progressed. Conversely, Bax protein (pro-apoptotic) was predominantly localized to the tubule Sertoli cells, whereas the germ cells were Bax immunonegative.

In conclusion, human fetal Leydig cell hyperplasia is characterized by increasing numbers of proliferating cells and increased expression of steroidogenic enzymes. The Bcl-2-positive, Bax-negative status of the peritubular myoid cells may be a strategy for cell survival.

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