A potential role for cadmium in the etiology of varicocele-associated 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.