Isolation and characterization of the primary structure of testis- specific L-type calcium channel: implications for contraception

Goodwin, Leslie O.; Leeds, Nina B.; Hurley, Ian; Mandel, Francine S.; Pergolizzi, Robert G.; Benoff, Susan

doi:10.1093/molehr/3.3.255

Cited by 81 publications

(79 citation statements)

References 17 publications

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“…221), suggesting that these channels may be present in an electrophysiologically inactive state and activated during sperm differentiation and maturation.…”

Section: Ca V Channels In Spermatogenic Cells and Spermatozoamentioning

confidence: 99%

Calcium Channels in the Development, Maturation, and Function of Spermatozoa

Darszon

Nishigaki

Beltrán

et al. 2011

Physiological Reviews

314

313

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-permeable channels and located them at distinct sites in spermatozoa so that they can help fertilize the egg. New tools to study sperm ionic currents, and image intracellular Ca 2ϩ with better spatial and temporal resolution even in swimming spermatozoa, are revealing how sperm ion channels participate in fertilization. This review critically examines the involvement of Ca 2ϩ channels in multiple signaling processes needed for spermatozoa to mature, travel towards the egg, and fertilize it. Remarkably, these tiny specialized cells can express exclusive channels like CatSper for Ca 2ϩ and SLO3 for K ϩ , which are attractive targets for contraception and for the discovery of novel signaling complexes. Learning more about fertilization is a matter of capital importance; societies face growing pressure to counteract rising male infertility rates, provide safe male gamete-based contraceptives, and preserve biodiversity through improved captive breeding and assisted conception initiatives.

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“…221), suggesting that these channels may be present in an electrophysiologically inactive state and activated during sperm differentiation and maturation.…”

Section: Ca V Channels In Spermatogenic Cells and Spermatozoamentioning

confidence: 99%

Calcium Channels in the Development, Maturation, and Function of Spermatozoa

Darszon

Nishigaki

Beltrán

et al. 2011

Physiological Reviews

314

313

View full text Add to dashboard Cite

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“…Secondly, CCB may mimic gossypol, a binaphthalendialdehyde extracted from cotton seeds in its effects on sperm function. Gossypol as an antifertility agent has an efficacy rate of 98.9% and does not affect production of testosterone and luteinizing hormones [11]. Because of the lipophilic nature of gossypol, it interacts directly with the phospholipid bilayer of biological membranes altering membrane structure, electrostatic charges and transmembrane ion fluxes.…”

Section: Discussionmentioning

confidence: 99%

“…-ATPase activities in ram and bull sperm plasma membrane vesicles [13]. In many respects, CCB effects changes on sperm membrane structure and functions similar to those of gossypol [10,11]. These changes include blocking mannose lectins (an important binding protein on the sperm membrane) from moving to the surface of the cell membrane thereby leading to excess cholesterol on the sperm head and stiffening of the membrane, thus affecting the normal movement of the sperm [10,11,28].…”

Section: Discussionmentioning

confidence: 99%

“…In males, LH stimulates the production of testosterone from the leydig cells and testosterone is absolutely required for spermatogenesis. It is known that potent anti-fertility agents do not necessary affect production of testosterone and luteinizing hormones [11]. Therefore, it appears that the primary site of action of these calcium channel blockers is not on the hypothalamic-pituitary-testicular axis, but rather may be directly on the reproductive tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

“…There have been reports of reversible functional defects in sperm, and inability to fertilize eggs with standard semen analysis parameters in hypertensive patients taking CCB [10,11]; however, a contrary report exists [12]. The antifertility effects of nifedipine and similar CCB are wellunderstood in in vitro experiments [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Antireproductive effect of calcium channel blockers on male rats

Morakinyo

Iranloye

Adegoke

2009

Reprod Medicine & Biology

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Introduction Drugs have been shown to adversely affect male fertility and recently anti-hypertensive drugs were added to the list. The anti-fertility effects of nifedipine and similar calcium channel blockers are well-illustrated in in vitro experiments but not in vivo. Purpose The present study was designed to experimentally elucidate the sub-chronic effect of nifedipine, verapamil and diltiazem on sperm functions and reproductive hormone levels in vivo. Methods Male rats (150-200 g) were divided into four groups of ten rats each. Group 1 (control) received distilled water; Group 2 received nifedipine 0.57 mg/kg BW; Group 3 were given verapamil 3.40 mg/kg BW and Group 4 were given diltiazem 2.57 mg/kg BW. Each drug-treated group had its own recovery group from which treatment was discontinued for 30 days before the animals were sacrificed. Blood samples were collected for hormonal assay of FSH, LH and testosterone. Semen evaluation was done and the testes, seminal vesicle, epididymis and prostate were removed, and weighed immediately. Results Nifedipine, verapamil and diltiazem significantly decreased (P \ 0.05) sperm count and motility in drug treated groups. The weight of the epididymis was significantly reduced (P \ 0.05) in the drug treated rats. Semen parameters and other associated changes were restored after 30 days of drug withdrawal.Conclusion Calcium channel blockers appear to have a reversible anti-fertility effect on male rats which does not occur through inhibition of the pituitary-gonadal axis.

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