THE EFFECT OF CALCIUM-ION CHANNEL BLOCKERS ON SPERM FERTILIZATION POTENTIAL

Objective: To evaluate the effects of calcium ion (Ca2+) channel block ers on male fertility potential. Design: A case comparison of the surf ace expression of mannose-ligand receptors on motile spermatozoa from 10 known fertile males and from 10 normospermic men taking Ca2+ channe l 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 univ ersity 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 Me asures: 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. S perm were assayed before and after an 18-hour or 3-day incubation unde r capacitating conditions in vitro. Results: Motile spermatozoa of nor mospermic men taking calcium antagonists for hypertension control do n ot express head-directed mannose-ligand receptors at high frequency, n or do they undergo spontaneous acrosome loss. Unexpectedly, mannose-li gand receptor translocation from the subplasmalemmal space over the ac rosome to the sperm surface and aggregation over the equatorial-postac rosomal regions occurred in acrosome-intact sperm. This differs from f ertile controls in whom receptor translocation to the equatorial-posta crosomal segment is coupled with the acrosome reaction (AR). Discontin uation of calcium antagonists results in complete recovery of paramete rs associated with sperm fertilizing potential: time-dependent increas es in the percentages of spermatozoa exhibiting surface mannose-ligand binding and spontaneous ARs in vitro. The effects of in vivo administ ration of calcium antagonists is mimicked in control fertile donor spe rm 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 in fertility associated with an IVF failure. A mechanism of inhibition of sperm fertilizing potential through insertion of lipophilic calcium i on antagonists into the lipid bilayer of the sperm plasma membrane is consistent with our in vitro studies.