Differential expression of apoptotic proteins in seminiferous tubule cells of adult rats by neonatal exposure to 6-n-propyl-2-thiouracil (PTU), a thyroid disrupting chemical

Abstract

Role of thyroid hormones in the development of testis is still a matter of debate. Previously, we have shown that spermatogenesis is impaired in adult rats by 6-n-propyl-2-thiouracil (PTU)-induced neonatal hypothyroidism. This was accompanied by augmentation of oxidative stress and modification of the expression of antioxidant defence enzymes in seminiferous tubule cells (STCs) of adult rats. In the present study, we sought to further elucidate the role of neonatal hypothyroidism on the development of testis by investigating the expression of some pro- and anti- apoptotic proteins in adult testicular STCs of rats exposed to PTU from birth because recent studies have demonstrated a pivotal role of oxidative stress in apoptosis.Neonatal PTU treatment has resulted in upregulation of pro-apoptotic genes such as <em>Bax</em>, <em>Bad</em>, <em>caspase-3</em> and <em>p53</em> in seminiferous tubule cells in adulthood. Withdrawal of PTU treatment on 30 days of age failed to restore the expression of pro-apoptotic genes in seminiferous tubule cells to that of controls. Expression of Bcl-2 did not change in response to PTU treatment. This study reveals that transient and persistent neonatal hypothyroidism resulted in permanent upregulation of pro-apoptotic genes in rat seminiferous tubule cells in adulthood which may impair testicular physiological functions.