Multiple effects of retinoids on the development of Sertoli, germ, and Leydig cells of fetal and neonatal rat testis in culture

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), Addi tion 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 Sert oli cells. RA caused no disorganization of older testes, but it did cause h yperplasia of the Sertoli cells in 3-dpp testes. Fragmentation of the Serto li cell DNA was not detected in control or RA-treated testes at any age stu died. The cAMP produced in response to FSH was significantly decreased in R A-treated testes for all studied ages. Both 10-6 M and 3.10-8 M RA dramatic ally reduced the number of gonocytes per 14.5-dpc testis, This resulted fro m a high increase in apoptosis, which greatly exceeded the slight increase of mitosis. RA caused no change in the number of gonocytes in testes explan ted 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 resum e). Lastly, RA and retinol (RE) reduced both basal and acute LH-stimulated testosterone secretion by 14.5-dpc testis explants, without change in the n umber of 3 beta-hydroxysteroid dehydrogenase-positive cells per testis. Ret inoids had no effect on basal or LH-stimulated testosterone production by o lder testes. In conclusion, RE and RA are potential regulators of the devel opment of the testis and act mainly negatively during fetal life and positi vely during the neonatal period on the parameters we have studied.