Complete Sperm Suppression in Rats With Dienogest Plus Testosterone Undecanoate Is Facilitated Through Apoptosis in Testicular Cells

Complete suppression of the production of sperm in rats with dienogest (DNG, 40 mg/kg body weight [bw]) plus testosterone undecanoate (TU, 25 mg/kg bw), every 45 days, was found to be associated with a significant increase in germ cell apoptosis. Caspase 3 activity and expression in testis were simultaneously upregulated. Rise in the activities of caspase 8 and 9 was associated with overexpression of upstream marker proteins from extrinsic (Fas [Fatty acid synthase], FasL [Fatty acid synthase ligand], and caspase 8) and intrinsic (Bax [Bcl2-associated-x protein], Bcl2 [B-cell lymphoma 2], and caspase 9) pathways of apoptosis. Apart from the germ cells, interstitial cell apoptosis was also observed along with a decline in the number of functional Leydig cells. It is therefore concluded that complete suppression of the production of sperm with DNG + TU is facilitated mainly through the removal of precursor germ cells through apoptosis. The process is largely modulated by upregulation of upstream and downstream marker proteins from intrinsic as well as extrinsic pathway of metazoan apoptosis.