OBJECTIVE: To evaluate the effects of calcium ion (Ca2+) channel blockers on male fertility potential. DESIGN: A case comparison of the surface expression of mannose-ligand receptors on motile spermatozoa from 10 known fertile males and from 10 normospermic men taking Ca2+ channel blockers who were seeking infertility treatment. Examination of the effects of in vitro exposure of sperm from fertile donors (n = 14) to antihypertensive medications. SETTING: Patients from a successful university hospital-based IVF-assisted reproductive technology program and from a male urology private practice. INTERVENTIONS: Prescription of alternate hypotensive medications for four male patients; cholesterol loading and unloading in vitro of fertile donor sperm. MAIN OUTCOME MEASURES: Motile sperm were tested for their ability to bind fluorescein isothiocyanate-labeled, mannosylated bovine serum albumin as an index of the surface expression of mannose-ligand receptors associated with fertility potential. Acrosome status was simultaneously evaluated by fluorescence microscopy with rhodamine-labeled Pisum sativum lectin. Sperm were assayed before and after an 18-hour or 3-day incubation under capacitating conditions in vitro. RESULTS: Motile spermatozoa of normospermic men taking calcium antagonists for hypertension control do not express head-directed mannose-ligand receptors at high frequency, nor do they undergo spontaneous acrosome loss. Unexpectedly, mannose-ligand receptor translocation from the subplasmalemmal space over the acrosome to the sperm surface and aggregation over the equatorial-postacrosomal regions occurred in acrosome-intact sperm. This differs from fertile controls in whom receptor translocation to the equatorial-postacrosomal segment is coupled with the acrosome reaction (AR). Discontinuation of calcium antagonists results in complete recovery of parameters associated with sperm fertilizing potential: time-dependent increases in the percentages of spermatozoa exhibiting surface mannose-ligand binding and spontaneous ARs in vitro. The effects of in vivo administration of calcium antagonists is mimicked in control fertile donor sperm by inclusion of a Ca2+ channel blocker in the media employed during capacitating incubations. CONCLUSIONS: Therapeutic administrations of calcium antagonists for hypertension control cause reversible male infertility associated with an IVF failure. A mechanism of inhibition of sperm fertilizing potential through insertion of lipophilic calcium ion antagonists into the lipid bilayer of the sperm plasma membrane is consistent with our in vitro studies.
OBJECTIVE: To evaluate the effects of calcium ion (Ca2+) channel blockers on male fertility potential. DESIGN: A case comparison of the surface expression of mannose-ligand receptors on motile spermatozoa from 10 known fertile males and from 10 normospermic men taking Ca2+ channel blockers who were seeking infertility treatment. Examination of the effects of in vitro exposure of sperm from fertile donors (n = 14) to antihypertensive medications. SETTING:Patients from a successful university hospital-based IVF-assisted reproductive technology program and from a male urology private practice. INTERVENTIONS: Prescription of alternate hypotensive medications for four male patients; cholesterol loading and unloading in vitro of fertile donor sperm. MAIN OUTCOME MEASURES: Motile sperm were tested for their ability to bind fluorescein isothiocyanate-labeled, mannosylated bovine serum albumin as an index of the surface expression of mannose-ligand receptors associated with fertility potential. Acrosome status was simultaneously evaluated by fluorescence microscopy with rhodamine-labeled Pisum sativum lectin. Sperm were assayed before and after an 18-hour or 3-day incubation under capacitating conditions in vitro. RESULTS: Motile spermatozoa of normospermic men taking calcium antagonists for hypertension control do not express head-directed mannose-ligand receptors at high frequency, nor do they undergo spontaneous acrosome loss. Unexpectedly, mannose-ligand receptor translocation from the subplasmalemmal space over the acrosome to the sperm surface and aggregation over the equatorial-postacrosomal regions occurred in acrosome-intact sperm. This differs from fertile controls in whom receptor translocation to the equatorial-postacrosomal segment is coupled with the acrosome reaction (AR). Discontinuation of calcium antagonists results in complete recovery of parameters associated with sperm fertilizing potential: time-dependent increases in the percentages of spermatozoa exhibiting surface mannose-ligand binding and spontaneous ARs in vitro. The effects of in vivo administration of calcium antagonists is mimicked in control fertile donor sperm by inclusion of a Ca2+ channel blocker in the media employed during capacitating incubations. CONCLUSIONS: Therapeutic administrations of calcium antagonists for hypertension control cause reversible male infertility associated with an IVF failure. A mechanism of inhibition of sperm fertilizing potential through insertion of lipophilic calcium ion antagonists into the lipid bilayer of the sperm plasma membrane is consistent with our in vitro studies.