Neonatal hypothyroidism does not increase Sertoli cell proliferation in iNOS^-/- mice

Sertoli cell (SC) proliferation in mice occurs until two weeks after birth and is mainly regulated by FSH and thyroid hormones. Previous studies have shown that transient neonatal hypothyroidism in laboratory rodents is able to extend SC mitotic activity, leading ultimately to higher testis size and daily sperm production (DSP) in adult animals. Moreover, we have shown that due to higher SC proliferation and lower germ cell apoptosis, iNOS deficiency in mice also results in higher testis size and DSP. Although the cell size was smaller, the Leydig cells (LCs) number per testis also significantly increased in iNOS^-/- mice. Our aims in the present study were to investigate if the combination of neonatal hypothyroidism and iNOS deficiency promotes additive effects in SC number, testis size and DSP. Hypothyroidism was induced in wild-type (WT) and iNOS^-/- mice using 6-propyl-2-thiouracil (PTU) through the mother's drinking water from 0 to 20 days of age, and were sacrificed at adulthood. Our results showed that, in contrast to the WT mice in which testis size, DSP and SC numbers increased significantly by 20, 40 and 70% respectively, after PTU treatment, no additive effects were observed for these parameters in treated iNOS^-/- mice, as well as for LC. No alterations were observed in spermatogenesis in any group evaluated. Although we still do not have an explanation for these intriguing findings, we are currently investigating whether thyroid hormones influence iNOS levels and/or counterbalance physiological effects of iNOS deficiency in testis function and spermatogenesis.