I.R. Hurley

A potential role for cadmium in the etiology of varicoceleassociated infertility

OBJECTIVE To determine whether mannose ligand receptor and acrosome reaction deficits in sperm from men with varicocele are related to the transition metal content of their semen. DESIGN Cadmium and zinc in semen and blood plasma were assayed for fertile males, men without varicocele who required intracytoplasmic sperm injection to achieve fertilization, and men evaluated for potential varicocele-associated infertility. The relationship between actin cytoskeletal distributions and acrosome status was determined for fertile donor sperm in the presence and absence of exogenous cadmium. SETTING University hospital-based molecular biology research laboratory. PATIENT(S) Patients from two university hospital-based IVF-assisted reproductive technology programs and two male urology private practices. INTERVENTION(S) Fertile donor sperm were exposed to exogenous cadmium during capacitating incubations followed by culture at temperatures up to 41 degrees C. MAIN OUTCOME MEASURE(S) Metal ion levels in semen and blood plasma were determined by graphite furnace atomic absorption spectroscopy. Motile sperm were examined for mannose ligand binding and the ability to undergo spontaneous and induced acrosome reactions. Unfixed, Triton-permeabilized sperm were probed with antiactin and antimyosin antibodies. RESULT(S) Cadmium was elevated and zinc was decreased in the seminal plasma of men with varicocele. The content of these metals in semen and blood was not correlated. Cadmium exposure in vitro reduced mannose receptor expression, acrosome exocytosis, and cytoskeletal formation by fertile donor sperm. CONCLUSION(S) Defects in transition metal regulation or excessive cadmium exposure are involved in varicocele-associated infertility.

Metal ions and human sperm mannose receptors

Zinc and lead concentrations were measured in seminal plasma from fertile donors, infertile men with varicocoele and men undergoing work‐ups for in vitro fertilization. Ejaculated spermatozoa from these subjects were incubated in vitro with various metal ions and/or dibromoethane and dibromochloropropane. Mannose receptor expression was correlated with metal and toxicant levels. Sperm distributions of potassium channels were compared with lead ions and calcium channels with zinc ions. Mannose receptor expression by capacitated spermatozoa increased linearly with seminal plasma zinc levels, and correlated inversely with lead levels. Cobalt had no effect on mannose receptor expression, but nickel had a concentration‐dependent biphasic effect. Mannose receptor expression was not affected by dibromoethane and dibromochloropropane if the cholesterol content of the sperm membrane was high, but mannose receptor expression was decreased in low cholesterol spermatozoa by exposures below estimated permissive exposure limits. Potassium channels and lead ions co‐localized over the entire head of human spermatozoa, while both calcium channels and zinc ions were confined to the equatorial segment of the head. Mannose receptor expression on the external surface of the human sperm plasma membrane is a biomarker for the effects of transition and heavy metals and organic toxicants on sperm fertility potential.

Numerical dose-compensated in vitro fertilization inseminations yield high fertilization and pregnancy rates

OBJECTIVE To evaluate in cases with morphologically abnormal sperm whether fertilization and pregnancy rates are increased by normalizing the number of sperm inseminated and whether biomarkers can identify cases of reduced or failed fertilization. DESIGN Prospective studies of sperm morphology and function. SETTING University hospital assisted human reproduction program. PATIENT(S) Partners of 308 women undergoing IVF. INTERVENTION(S) Motile sperm populations were assessed for sperm head morphology, for surface receptors for mannose and progesterone binding, and the ability to undergo a free mannose-induced acrosome reaction. Zinc in seminal plasma was determined by atomic absorption spectroscopy. MAIN OUTCOME MEASURE(S) Sperm morphology was associated with fertilization and clinical pregnancy rates. Biomarker analyses were correlated with fertilization rates using Kruskal-Wallis tests, chi2 tests, and Spearman rank order correlations. RESULT(S) Fertilization and pregnancy rates after numerical dose compensation inseminations were indistinguishable between men with differing percentages of normal sperm. Biomarker deficits were identified irrespective of sperm head morphology in 96% of cases of reduced or failed fertilization. CONCLUSION(S) Fertilization and pregnancy rates in cases of abnormal morphology are optimized by inseminating at least 25,000 sperm/mL with normal acrosomes. Reduced or failed fertilization can be predicted by testing for molecular deficits in mannose receptor expression and mannose-stimulated acrosome loss.