Verapamil‐induced ion channel and miRNA expression changes in rat testis and/or spermatozoa may be associated with male infertility

Abstract

Verapamil, a prototypical phenylalkylamine, is the clinically first used Ca 2+ channel blocker (CCB). It is known to be an effective drug in the treatment of hypertension (Bergson, Lipkind, Lee, Duban, & Hanck, 2011). However, due to the fact that an ion channel type is often expressed in many cell types, an important side effect of such drugs may occur negatively affecting normal function in nondiseased tissues (Conte Camerino & Desaphy, 2010). Mature spermatozoa are produced in spermatogenesis which is a multi-stage and tightly controlled process. Disrupted regulatory mechanisms in spermatogenesis can cause many diseases, from male fertility to cancer. In infertile men, impaired spermatogenesis may be related to several aetiologies and precise molecular mechanisms are unknown (Khawar, Mehmood, & Roohi, 2019). microRNAs (miRNA), which regulate gene expression by blocking protein translation or inducing mRNA degradation, are short noncoding RNA sequences (Akkina & Becker, 2017). On the other

First emerging evidence of the relationship between Onuf’s nucleus degeneration and reduced sperm number following spinal subarachnoid haemorrhage: Experimental study

“…We did not evaluate the sperm concentration, motility and morphology (Tektemur et al, 2020), vitality (Banihani & Shatnawi, 2020 as in the previous studies, but found an important finding which is a reduced mean sperm numbers may occur following the spinal SAH. The histological view of seminiferous tubules of a control group animal in Figure 4a, and atrophic seminiferous tubules with deformed spermatids and apoptotic spermatids and constructed-oedematous testicular artery of a rabbit with SAH are seen in Figure 4c.…”

The Possible Role of Prescribing Medications, Including Central Nervous System Drugs, in Contributing to Male-Factor Infertility (MFI): Assessment of the Food and Drug Administration (FDA) Pharmacovigilance Database

“…Calcium ions are vital second messengers in human physiology, and the use of drugs that interfere with their function may potentially lead to an interference with a number of biological pathways, thus including spermatogenesis. Even though reduced sperm concentration, impaired serum testosterone, FSH and LH levels were associated with verapamil exposure in a number of preclinical studies on rats [71,72], well-designed observational studies and RCTs to define this association in the clinical setting are still lacking. Calcium channels are highly represented in mature sperm cells, and interference with these may potentially lead to an interference with some of the sperm-egg fertilization processes, such as the acrosome reaction [71].…”

“…Even though reduced sperm concentration, impaired serum testosterone, FSH and LH levels were associated with verapamil exposure in a number of preclinical studies on rats [71,72], well-designed observational studies and RCTs to define this association in the clinical setting are still lacking. Calcium channels are highly represented in mature sperm cells, and interference with these may potentially lead to an interference with some of the sperm-egg fertilization processes, such as the acrosome reaction [71]. Calcium ions are also needed for the epididymal acquisition of sperm motility in experimental models [73].…”

Association between Sperm Morphology and Altered Sperm microRNA Expression

“…Studies have shown that paternal obesity and dietary changes contribute crucially to miRNA dysregulation in spermatozoa, which may also further dictate offspring metabolism [ 9 , 10 ]. Similarly, alterations in miRNA expression, associated with decreased fertility in males, have been determined in sperm and seminal plasma from patients using prescription drugs and illegal substances, including verapamil [ 11 ] and heroin [ 12 ], respectively. In addition, a study by Jia et al on animal models discovered miRNAs the expression profiles of which differed in relation to the age of the animals [ 13 ], which suggested that such interrelations could also apply in humans.…”