Effects of L- and T-type Ca²(+) channel blockers on spermatogenesis and steroidogenesis in the prepubertal mouse testis.
OBJECTIVE
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.
Lee
Jae Ho
JH
Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, 330-714, South Korea.
Ahn
Hak Jun
HJ
Lee
Sang Jin
SJ
Gye
Myung Chan
MC
Min
Churl K
CK
D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000378:metabolism; D005013:Ethosuximide / Q000009:adverse effects*; D007248:Infertility, Male / Q000139:chemically induced; D007985:Leydig Cells / Q000166:cytology; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009543:Nifedipine / Q000009:adverse effects*; D009929:Organ Size; D010750:Phosphoproteins / Q000378:metabolism; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D000098682:Steroidogenic Acute Regulatory Protein
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D005013:Ethosuximide; D007986:Luteinizing Hormone; D009543:Nifedipine; D002118:Calcium