TRANSFORMING-GROWTH-FACTOR BETA-1 AND BETA-2 REDUCE THE NUMBER OF GONOCYTES BY INCREASING APOPTOSIS

Transforming growth factors beta 1 and beta 2 (TGF beta s) have recent ly been detected by immunohistochemistry in the fetal and neonatal rat testis, and the aim of the present study was to determine whether the se factors can act as local regulators to control the number of gonocy tes. Testes were kept in organ culture, and TGF beta 1 was found to ha ve dose-dependent inhibitory effect on the number of gonocytes in test es explanted on fetal day 13.5. Either TGF beta 1 or beta 2 at 10 ng/m l reduced the number of gonocytes by half after 2 days culture. TGF be ta s did not decrease the BrdU labeling index of gonocytes or Sertoli cells, whereas these factors significantly increased the DNA fragmenta tion in gonocytes (TUNEL method). The other testicular cell types show ed no postive TUNEL reaction. TGF beta 1 did not reduce the number of gonocytes in testes explanted on fetal day 17.5 (i.e. during the quies cent phase), but it did so in testes explanted on postnatal day 3 (i.e . stage of resumption of mitosis). To determine the potential cell typ e targets for TGF beta s, type I and type II TGF beta receptors were i mmunolocalized in developing testis from fetal day 13.5 to postnatal d ay 3. Both receptors were present in the gonocytes throughout the whol e 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 TGF beta s directly increase apoptosis in gonocy tes without changing their mitotic activity during the developmental p hases of proliferation.