Objective-To define the mechanism(s) underlying an association between asthenozoospermia and elevated blood, seminal plasma and testicular cadmium levels in infertile human males using a rat model of environmentally relevant cadmium exposures.Setting-University medical center andrology research laboratory.
Animals-MaleWistar rats (n = 60), documented to be sensitive to the testicular effects of cadmium.Interventions-Rats were given ad libitum access to water supplemented with 14% sucrose and 0, 5, 50 or 100 mg/L cadmium for 1, 4 or 8 weeks being at puberty.Main outcome measure(s)-Testicular cadmium levels were determined by atomic absorption, cauda epididymal sperm motility by visual inspection, and testicular gene expression by DNA microarray hybridization.Results-Chronic, low dose cadmium exposures produced a time-and dose-dependent reduction in sperm motility. Transcription of genes regulated by calcium and expression of L-type voltagedependent calcium channel mRNA splicing variants were altered by cadmium exposure. Expression of calcium binding proteins involved in modulation of sperm motility was unaffected. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Presented at the UCSF-CHE Summit on Environmental Challenges to Reproductive Health and Fertility, UCSF Mission Bay Conference Center, San Francisco, California, January 28-30, 2007. NIH Public Access Conclusions-A causal relationship between elevated testicular cadmium and asthenozoospermia was identified. Aberrrant sperm motility was correlated with altered expression of L-type voltagedependent calcium channel isoforms found on the sperm tail, which regulate calcium and cadmium influx.