Effects of L- and T-type Ca²(+) channel blockers on spermatogenesis and steroidogenesis in the prepubertal mouse testis

型和 T 型 Ca²(+) 通道阻滞剂对青春期前小鼠睾丸精子发生和类固醇生成的影响

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作者:Jae Ho Lee, Hak Jun Ahn, Sang Jin Lee, Myung Chan Gye, Churl K Min

Conclusions

Both T- and L-type Ca²(+) channel blockers play an adverse role in normal spermatogenesis and steroidogenesis partly by blocking postmeiotic germ cell maturation and/or by abrogating StAR protein expression, contributing to male sterility. Therefore, any therapeutic application of Ca²(+) channel blockers must be used with caution due to its potential adverse side effects on male infertility.

Methods

Prepubertal male mice were fed Ca²(+) channel blockers nifedipine and ethosuximide for 20 days at dosages below maximum tolerated dose (MTD) and assayed for gross morphological changes in the testis such as body weight, testis size and weight. Sperm and Leydig cell counting were conducted concomitantly with serum testosterone level measurement by radioimmunoassay (RIA) and StAR protein mRNA measurement by reverse transcription and polymerase chain reaction (RT-PCR).

Purpose

To assess the involvement of L-type and T-type Ca²(+) channel blockers in inducing male infertility.

Results

A chronic exposure to nifedipine or ethosuximide caused a significant reduction in body weight, testis size/weight and sperm production in a dose-dependent fashion associated with a spermatogenic arrest largely at the elongating spermatid stage. The number of Leydig cells, the serum testosterone level but not the luteinizing hormone level, and the content of StAR protein mRNA were also drastically reduced relative to the controls. Conclusions: Both T- and L-type Ca²(+) channel blockers play an adverse role in normal spermatogenesis and steroidogenesis partly by blocking postmeiotic germ cell maturation and/or by abrogating StAR protein expression, contributing to male sterility. Therefore, any therapeutic application of Ca²(+) channel blockers must be used with caution due to its potential adverse side effects on male infertility.

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