Cyclopiazonic acid induced p53-dependent apoptosis in the testis of mice: Another male related risk factor of infertility.

Cyclopiazonic acid (CPA) is an indole tetrameric acid mycotoxin. This study carried out to investigate the potential effects of CPA on male reproductive system. In the current study, 40 adult male mice were divided into five groups (n = 8). The control group did not expose to CPA, while animals in vehicle-received group; received the CPA-solvent (0.05% dimethyl sulfoxide) and the animals of third, fourth, and fifth groups received CPA 0.03, 0.06, and 0.12 mg/kg, body weight, respectively for 28 days. Morphometric and morphological deviations, spermatogenesis indices, malondialdehyde (MDA) content, total thiol molecules (TTM) concentration, total antioxidant capacity (TAC), protein carbonylation rate (CO), and nitric oxide (NO) concentration were examined. The expression changes of apoptotic genes (P53, Bcl-2, and Caspase III) at mRNA level were also evaluated by qPCR technique. Reduction in the Leydig and Sertoli cells population, diameter of seminiferous tubules, and spermatogenesis parameters was significant only in the group that received the highest dose of CPA. An increase in the level of MDA, NO, and CO in testicular tissue and reduction of TAC and TTM were observed in the CPA-exposed groups. Significant up-regulation (p < .05) in the expression of P53 and Caspase III genes and down-regulation of Bcl-2 gene were found in the CPA-received groups. These results are indicating the detrimental effects of CPA on the testicles, which may attribute to the CPA-induced oxidative stress and apoptosis. Moreover, results also help to understand a serious concern about the presence of CPA in foods as a potential risk factor in male-related infertility.