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Human Spermatogenesis in Vitro: Respective Effects of Follicle-Stimulating Hormone and Testosterone on Meiosis, Spermiogenesis, and Sertoli Cell Apoptosis

Laboratoire d’Eylau (J.T.), 75116 Paris, France; Department of Obstetrics and Gynecology (M.G.), Università Cattolica del Sacro Cuore, 00168 Rome, Italy; Department of Biochemistry and Molecular Biology (C.M.), University of Granada Faculty of Sciences, 18071 Granada, Spain; and Center of Reproductive Medicine, European Hospital (E.G.), 00149 Rome, Italy

Address all correspondence and requests for reprints to: Dr. Jan Tesarik, Laboratoire d’Eylau, 55 Rue Saint-Didier, 75116 Paris, France.

In spite of the availability of abundant data about in vitro spermatogenesis in laboratory animals, studies on human in vitro spermatogenesis are scarce. This study employed a relatively simple culture system, involving all cell types of seminiferous tubules, to analyze the effects of FSH and testosterone (T) on different characteristics of human germ and Sertoli cells in culture. By using fluorescence in-situ hybridization, we show that in vitro reduction of germ cell ploidy can be stimulated by FSH but not by T. FSH, but not T, also induced unexpectedly rapid (24–48 h) morphological changes resembling spermiogenesis, although individual changes (spermatid nucleus condensation and protrusion, cell body elongation, and flagellar growth) proceeded in an uncoordinated way and mostly resulted in the development of abnormal forms of elongated spermatids. Though ineffective alone, T potentiated the effects of FSH on meiosis and spermiogenesis. These effects of T were probably caused by the prevention of Sertoli cell apoptosis, an effect that could not be mimicked by FSH. These data show that, in the presence of high concentrations of FSH and T, human spermatogenesis can proceed in vitro with an unusual speed, but the resulting gametes are morphologically abnormal. The potential practical relevance of these findings to assisted reproduction remains to be assessed.

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