Influence of antifertility agents Dutasteride and Nifedipine on CatSper gene level in epididymis during sperm maturation in BALB/c mice

Abstract

Calcium (Ca) signaling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility and the acrosome reaction are all mediated by increases in intracellular Ca through CatSper (sperm-specific cation channel). The CatSper channel complex contains four pore-forming α subunits (CatSper1-4) and five accessory subunits called β, δ, ε, γ and ζ. Genetic deletion of any of the four genes in mice results in loss of hyperactivated motility and male infertility. Despite their vital role in male fertility, almost very little is known about influence of antifertility agents on gene expression in epididymis and epididymal spermatozoa. Therefore, we performed quantitative real-time qPCR analysis for expression in the epididymis and epididymal sperm of BALB/c mice after treatment with Dutasteride (DS), a dual 5-α reductase inhibitor and Nifedipine (NF) a calcium channel blocker as positive control. We observed that treatment with antifertility agents Dutasteride and Nifedipine induced significant decreases in the caput and cauda epididymal sperm counts, motility and fertility which could partly be attributed to alteration in the normal morphology of the sperm associated with downregulation/upregulation of mRNAs in epididymis and epididymal spermatozoa of male BALB/c mice. These can be explained on the basis of interference with mechanisms affecting calcium ion signaling resulting in changes in intracellular calcium required for sperm activity, finally affecting sperm maturation and fertility of male BALB/c mice. These studies provide some novel avenues for developing new male contraceptives in future.

The Chemosensing Role of CatSper in Mammalian Sperm: An Updated Review

“…Thus, they interfere with Ca 2+ signaling mediated by PGs and P4. In addition, the exposure of mice to DS affected sperm count and motility and the expression of CatSper genes in caput and caudal epididymal sperm [ 75 ].…”

“…It exhibits anti-fertility effects in male rats, resulting in a significant reduction in sperm motility and count [ 78 ]. Nifedipine treatment reduces sperm motility and count and substantially downregulates the expression of CatSper genes in mouse epididymal sperm [ 75 ]. In addition, RU1968, a steroid-based selective and potent cross-species inhibitor of CatSper, has been demonstrated to suppress the activation of CatSper in human, mouse, and sea urchin sperm [ 79 ].…”