Link between low-dose environmentally relevant cadmium exposures and asthenozoospermia in a rat model.
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.


METHODS
University medical center andrology research laboratory.


METHODS
Male Wistar rats (n = 60), documented to be sensitive to the testicular effects of cadmium.


METHODS
Rats were given ad libitum access to water supplemented with 14% sucrose and 0 mg/L, 5 mg/L, 50 mg/L, or 100 mg/L cadmium for 1, 4, or 8 weeks beginning at puberty.


METHODS
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 voltage-dependent calcium channel mRNA splicing variants were altered by cadmium exposure. Expression of calcium binding proteins involved in modulation of sperm motility was unaffected.


CONCLUSIONS
A causal relationship between elevated testicular cadmium and asthenozoospermia was identified. Aberrrant sperm motility was correlated with altered expression of L-type voltage-dependent calcium channel isoforms found on the sperm tail, which regulate calcium and cadmium influx.
Benoff
Susan
S
Fertility Research Laboratories, The Feinstein Institute for Medical Research, Manhasset, New York 11030, USA. Sbenoff@nshs.edu
Auborn
Karen
K
Marmar
Joel L
JL
Hurley
Ian R
IR
D017398:Alternative Splicing / Q000187:drug effects; D000818:Animals; D053627:Asthenozoospermia / Q000139:chemically induced* / Q000503:physiopathology; D002104:Cadmium / Q000097:blood / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013081:Sperm Motility / Q000187:drug effects; D013737:Testis / Q000187:drug effects*
D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D004785:Environmental Pollutants; D012333:RNA, Messenger; D002104:Cadmium; D002118:Calcium