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a Université Paris 7 and INSERM-INRA U 418, Tour 33/43, case 7126, 75251 Paris Cedex 05, France
b INSERM-INRA U 418, Hôpital Debrousse, 69222 Lyon, France
We investigated the effect of retinoids on the development of Sertoli, germ, and Leydig cells using 3-day culture of testes from fetuses 14.5 and 18.5 days post-conception (dpc) and from neonates 3 days postpartum (dpp). Addition of 10-6 M and 3.10-8 M retinoic acid (RA) caused a dose-dependent disruption of the seminiferous cords in 14.5-day-old fetal testes, without any change in the 5-bromo-2'-deoxyuridine (BrdU) labeling index of the Sertoli cells. RA caused no disorganization of older testes, but it did cause hyperplasia of the Sertoli cells in 3-dpp testes. Fragmentation of the Sertoli cell DNA was not detected in control or RA-treated testes at any age studied. The cAMP produced in response to FSH was significantly decreased in RA-treated testes for all studied ages. Both 10-6 M and 3.10-8 M RA dramatically reduced the number of gonocytes per 14.5-dpc testis. This resulted from a high increase in apoptosis, which greatly exceeded the slight increase of mitosis. RA caused no change in the number of gonocytes in testes explanted on 18.5 dpc (the quiescent period), whereas it increased this number in testes explanted on 3 dpp (i.e., when gonocyte mitosis and apoptosis resume). Lastly, RA and retinol (RE) reduced both basal and acute LH-stimulated testosterone secretion by 14.5-dpc testis explants, without change in the number of 3ß-hydroxysteroid dehydrogenase-positive cells per testis. Retinoids had no effect on basal or LH-stimulated testosterone production by older testes. In conclusion, RE and RA are potential regulators of the development of the testis and act mainly negatively during fetal life and positively during the neonatal period on the parameters we have studied.
1 This work was supported by INSERM, INRA, and Université Paris 7. G.L. holds a fellowship from the Ministère de l'Education Nationale de la Recherche et de la Technologie. Part of this study was presented in XVe Congrès de la Société d'Andrologie de Langue Française in Lyon on December 10–12th 1998.
2 Correspondence: René Habert, INSERM U 418—Université Paris 7, Tour 33/43, 2 Place Jussieu, 75251 Paris Cedex 05, France. FAX: 33 1 44 27 56 11; habert{at}paris7.jussieu.fr
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