Opioid-mediated Sertoli cells apoptosis is involved in testicular homeostasis and/or reproductive dysfunction

The opioid system may exert positive direct and/or indirect effects on spermatogenesis at multiple levels including the levels of the central nervous system and at the testes/sperm levels. However, long term opioid use could be associated with several reproductive complications that place the users at risk of hypogonadism and even infertility. There is little available information regarding the contribution of opioids and their apoptotic effects on testis Sertoli cells. Here, the effects of DAMGO (mu opioid receptor's agonist), DPDPE (delta opioid receptor's agonist) and DYN 1-9 (kappa opioid receptor's agonist) on Sertoli cell viability and apoptosis were investigated.

Cultured Sertoli cells were exposed to each agonist (0.1-100 µM, for 24 or 48 hours) and their apoptotic effects were investigated.

Cell viability was decreased and apoptosis was increased in the cells exposed to DAMGO in a concentration-dependent manner, while in the cells exposed to DPDPE, no significant changes were observed. In cells exposed to DYN 1-9, the viability did not significantly change, however apoptosis increased significantly, following the exposure to the high concentration of DYN 1-9.

These data suggest that mu and Kappa, but not delta receptors mediated apoptosis in Sertoli cells may be involved, at least in part, in testicular homeostasis and/or reproductive dysfunction (Tab. 1, Fig. 3, Ref. 52).