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Use of Organ Culture to Study the Human Fetal Testis Development: Effect of Retinoic Acid

Commissariat à l’Energie Atomique, Direction des Sciences du Vivant/Departement de Radiobiologie et Radioprotection/Service d’Etude de la Gamétogenèse et de la Génotoxicité/Laboratory of Differentiation and Radiobiology of the Gonads (R.L., H.C., C.P., R.H., V.R.-F.), Unit of Gametogenesis and Genotoxicity, Institut National de la Santé et de la Recherche Médicale U566 (R.L., H.C., C.P., R.H., V.R.-F.), and University of Paris 7 Denis Diderot (R.L., H.C., C.P., R.H., V.R.-F.), Unité de Formation et Recherche of Biology, F-92265 Fontenay-aux-Roses, France; Assistance Publique-Hôpitaux de Paris (A.-C.D., R.F.), Groupement Hospitalier Universitaire Sud, Hôpital A. Béclère, Service de Gynécologie-Obstétrique, F-92141 Clamart, France; and Institut Federatif de Recherche 13 (R.L., H.C., C.P., A.-C.D., R.F., R.H., V.R.-F.), F-92141 Clamart, France

Address all correspondence and requests for reprints to: Romain Lambrot, Institut National de la Santé et de la Recherche Médicale U 566, Commissariat à l’Energie Atomique, Université Paris 7, Route du Panorama BP 6, 92265 Fontenay-aux-Roses Cedex, France. E-mail: romain.lambrot{at}cea.fr; or virginie.rouiller-fabre{at}cea.fr.

Context: In human, the chronology of the testicular development has been extensively studied, but the factors implicated in the onset and the regulation of gametogenesis and steroidogenesis remain hardly known.

Objectives: To identify these factors, we developed an organ culture system for human fetal testes recovered during the first trimester (6–12 wk) of gestation. We first aimed at investigating the characteristics of this system by comparing the in vivo and in vitro gametogenesis and steroidogenesis. Second, we used organ culture to investigate the effect on the human testicular functions of retinoic acid (RA), previously described as a regulator of gonadal development in rodents.

Results: Organ culture proved to be an efficient tool for studying the early development of the testicular functions. Indeed, this system was able to maintain satisfactory development of the germ cells and Leydig cells in the absence of any added factor. For older fetuses, the number of germ cells decreased in culture and the LH was necessary to maintain the steroidogenic activity. The addition of 10^–6 M RA decreased the total number of germ cells in the fetal testis at all studied stages. This resulted from an increase in apoptosis, which slightly exceeded the increase of proliferation. However, RA had a stimulatory effect on the steroidogenic function for the youngest fetuses over a short period of time by increasing the expression of P450 cholesterol side-chain cleavage, 17 -hydroxylase/C17–20 lyase, and steroidogenic acute regulatory protein.

Conclusions: Thus, RA appears as a potential regulator of both gametogenesis and steroidogenesis in human fetal testis. Our organ culture is an interesting tool for studying the effects of various factors on the development of human fetal testis, in particular the effect of hormone-disrupting chemicals.

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