Downregulated StAR gene and male reproductive dysfunction caused by nifedipine and ethosuximide

Abstract

Steroid hormones that are controlled by steroidogenic acute regulatory (StAR) gene regulate sperm production. However, calcium ion is important for male fertility in vasodilation and sperm development. Calcium also serves as a second messenger to control acrosome reaction and sperm motility. Calcium channel-blockers (CCBs) as nifedipine and ethosuximide (used in hypertension and epilepsy treatment) can affect male fertility. However, little is known about the underlying mechanism of the male reproductive dysfunction and their side effects. The present study was designed to address the involvement of CCBs in inducing male infertility. Thirty-six male mice were orally treated by therapeutic dose of nifedipine and ethosuximide for 20 days followed by 10 days without treatment for drug withdrawal. Chromosome aberrations assay, sperm analysis and testicular expression level of biomarker steroidogenic acute regulatory (StAR (mRNA were measured. In addition, histological structure of the testis was investigated to the process of spermatogenesis. Our results revealed that, CCBs significantly increased the percentage of chromosome aberration and sperm shape change. StAR-mRNA expression was significantly down regulated. Sperm count and motility were significantly decreased. However, slight improvement was observed in all tested parameters after drug withdrawal. Seminiferous tubules displayed total atrophy, disruption, severe damage and elongation of tubules with disorganization of germinal epithelium that detached from the basement membrane. The lumen of seminiferous tubules showed complete absence of sperm cells.

Conclusions

Both nifedipine and ethosuximide significantly increase chromosome abnormalities, decrease sperm function, and down regulate StAR-mRNA expression. All these side effects may lead to irreversible male sterility.