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Transforming Growth Factor ß1 and ß2 Reduce the Number of Gonocytes by Increasing Apoptosis¹

INSERM-INRA U 418 (R.O., C.P., B.B., R.H.), Université Paris 7, Tour 33/43, 75251 Paris Cedex 05, France; INSERM-INRA U 418 (P.D.), Hôpital Debrousse, 69222 Lyon, France

Address all correspondence and requests for reprints to: Professor R. Habert, INSERM U 418, Université Paris 7, Tour 33/43, 2 Place Jussieu, 75251 Paris Cedex 05, France. E-mail: habert{at}paris7.jussieu.fr

Transforming growth factors ß1 and ß2 (TGFßs) have recently been detected by immunohistochemistry in the fetal and neonatal rat testis, and the aim of the present study was to determine whether these factors can act as local regulators to control the number of gonocytes. Testes were kept in organ culture, and TGFß1 was found to have dose-dependent inhibitory effect on the number of gonocytes in testes explanted on fetal day 13.5. Either TGFß1 or ß2 at 10 ng/ml reduced the number of gonocytes by half after 2 days culture. TGFßs did not decrease the BrdU labeling index of gonocytes or Sertoli cells, whereas these factors significantly increased the DNA fragmentation in gonocytes (TUNEL method). The other testicular cell types showed no positive TUNEL reaction. TGFß1 did not reduce the number of gonocytes in testes explanted on fetal day 17.5 (i.e. during the quiescent phase), but it did so in testes explanted on postnatal day 3 (i.e. stage of resumption of mitosis). To determine the potential cell type targets for TGFßs, type I and type II TGFß receptors were immunolocalized in developing testis from fetal day 13.5 to postnatal day 3. Both receptors were present in the gonocytes throughout the whole period studied, and in the Leydig cells from fetal day 16.5 onward, but they were not detected in the Sertoli cells. Taken together, these results suggest that TGFßs directly increase apoptosis in gonocytes without changing their mitotic activity during the developmental phases of proliferation.

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