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Effects of L- and T-type Ca²(+) channel blockers on spermatogenesis and steroidogenesis in the prepubertal mouse
Jae Ho Lee1, Hak Jun Ahn, Sang Jin Lee
1Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 330-714, South Korea.
Purpose:
To assess the involvement of L-type and T-type Ca²(+) channel blockers in inducing 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).
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.
Insights
Calcium channel blockers (nifedipine and ethosuximide) significantly impair male fertility by reducing sperm production and testosterone levels. These drugs can cause male infertility, necessitating caution during therapeutic use.
Area of Science:
- Reproductive Biology
- Endocrinology
- Pharmacology
Background:
- Calcium channels are crucial for male reproductive functions.
- L-type and T-type calcium channel blockers are widely used medications.
- Potential impact of these blockers on male fertility is not fully understood.
Purpose of the Study:
- To investigate the effects of L-type and T-type calcium channel blockers on male reproductive parameters.
- To assess the potential of these blockers in inducing male infertility.
Main Methods:
- Prepubertal male mice were treated with nifedipine (L-type) and ethosuximide (T-type) below maximum tolerated dose.
- Evaluated testis morphology, sperm count, Leydig cell count, serum testosterone, and StAR protein mRNA levels.
- Utilized radioimmunoassay (RIA) and reverse transcription-polymerase chain reaction (RT-PCR) for measurements.
Main Results:
- Chronic exposure to both blockers reduced body weight, testis size, and sperm production in a dose-dependent manner.
- Spermatogenesis was arrested at the elongating spermatid stage.
- Leydig cell number, serum testosterone, and StAR protein mRNA expression were significantly decreased.
Conclusions:
- Both L-type and T-type calcium channel blockers adversely affect spermatogenesis and steroidogenesis.
- These effects may be mediated by impaired postmeiotic germ cell maturation and reduced StAR protein expression.
- Therapeutic use of calcium channel blockers requires caution due to potential male infertility side effects.
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