SPERMATOGENESIS FOLLOWING DISCONTINUATION OF CALCIUM CHANNEL BLOCKER AMLODIPINE IN RATS
AbstractBackground: The calcium channel blockers are commonly associated with male infertility. Long termadministration of such drugs has been shown to suppress spermatogenesis. The present study wasdesigned to determine the effects of cessation of calcium channel blocker (amlodipine) medication onspermatogenesis. Methods: The study was carried out in the Department of Physiology, incollaboration with Department of Pathology, Army Medical College, and National Institute of Health,Islamabad from April 2007 to March 2008. Thirty male rats were divided into two groups A and B eachcontaining 15 rats. Group A rats were given distilled water (vehicle) whereas group B rats were givenamlodipine by oral gavage for 50 days. After 50 days, amlodipine/distilled water was withdrawn. Therats were left for recovery to take place for another 50 days of drug withdrawal period. Testes wereremoved in all the rats and sectioned. The sections were stained with haematoxylin and eosin andexamined microscopically. Results were analyzed using SPSS version 13. Results: Fifty days afterdrug withdrawal, there were statistically insignificant differences in mean tubular diameter and heightof germinal epithelium between amlodipine treated and vehicle treated groups. Conclusion:Spermatogenesis in amlodipine treated rats does not differ significantly from spermatogenesis invehicle treated rats after 50 days of drug withdrawal period.Keywords: Calcium channel blocker, CCB, amlodipine, male contraception, testicular histology,spermatogenesis, Dihydropyridine, DHP
Darszon A, Labarca P, Nishigaki T, Espinosa F. Ion channels
in sperm physiology. Physiol Rev 1999;79:481–510.
Stricker SA. Comparative biology of calcium signaling
during fertilization and egg activation in animals. Dev Biol
Kirkman-Brown JC, Punt EL, Barratt CL, Publicover SJ.
Zona pellucida and progesterone-induced Ca2+ signalling and
acrosome reaction in human spermatozoa. J Androl
Breitbart H. Intracellular calcium regulation in sperm
capacitation and acrosomal reaction. Mol Cell Endocrinol
Sakata Y, Saegusa H, Zong S, Osanai M, Murakoshi T,
Shimizu Y, et al. Ca(v)2.3 (alpha1E) Ca2+ channel
participates in the control of sperm function. FEBS Lett
Nikpoor P, Mowla SJ, Movahedin M, Ziaee SA, Tiraihi T.
CatSper gene expression in postnatal development of mouse
testis and in subfertile men with deficient sperm motility.
Hum Reprod 2004;19:124–8.
Carlson AE, Westenbroek RE, Quill T, Ren D, Clapham DE,
Hille B, et al. CatSper1 required for evoked Ca2+ entry and
control of flagellar function in sperm. Proc Natl Acad Sci
Suarez SS, Ho HC. Hyperactivated motility in sperm. Reprod
Domest Anim 2003;38:119–24.
Barratt CLR, Publicover SJ. Interaction between sperm and
zona pellucida in male fertility. Lancet 2001;358:1660–2.
Florman HM, Arnoult C, Kazam IG, Li C, O’Toole CM. A
perspective on the control of mammalian fertilization by eggactivated ion channels in sperm: a tale of two channels. Biol
Publicover SJ, Barratt CLR. Voltage-operated Ca2+ channels
and the acrosome reaction: which channels are present and
what do they do? Hum Reprod 1999;14:873–9.
Almaida SA, Teofilo JM, Franci JAA, Brentegani LG,
Carvalho TLL. Antireproductive effects of calcium channel
blocker Amlodipine in male rats. Exp Toxicol Pathol
Meacham RB. The Effect of Calcium Channel Blockers on
Male Reproductive Potential. J Androl 2006;27(2):160–5.
Latif R, Lodhi GM, Aslam M. Effects of amlodipine on
serum testosterone, testicular weight and gonado-somatic
index in adult rats. J Ayub Med Coll Abbottabad
Latif R, Aslam M, Hussain MM, Butt IF, Mubarik A, Zubair
A. Effects of amlodipine besylate on spermatogenesis in
Sprague Dawley rats. Pak Armed Forces Med J
Hershlag A, Cooper GW, Benoff S. Pregnancy following
discontinuation of a calcium channel blocker in the male
partner. Hum Reprod 1995;10:599–606.
Benoff S, Cooper GW, Hurley I, Mandel FS, Rosenfeld DL,
Scholl GM, et al. The effect of calcium ion channel blockers
on sperm fertilization potential. Fertil Steril 1994;62:606–17.
Kate Johnson. Calcium Channel Blocker as a Male
Contraceptive–Brief Article–Statistical Data Included. Family
Pratice News Feb 1, 2000. Available at:
Clermont Y, Harvey SC. Duration of the cycle of the
seminiferous epithelium of normal, hypophysectomizedhormone treated albino rats. Endocrinology 1965;76:80–9.
Working PK. Male reproductive toxicology: Comparison of
the human to animal models. Environ Health Perspect