March 2003

U.S. Researchers Link Lead, Male Infertility

Researchers have concluded that exposure to lead damages sperm function and may be a cause of unexplained male infertility.

The principal investigator of the new study, Susan Benoff, director of the Fertility Research Laboratories at North Shore-Long Island Jewish Research Institute in New York, suggested environmental exposure limits for lead should be re-evaluated. Funding for the study was provided by the National Institutes of Environmental Health Sciences, one of the National Institutes of Health. NIEHS had provided funding for Benoff's research for several years.

There are no apparent explanations for infertility in 5 to 10 percent of infertile couples, but the mean concentration of lead in soft tissues and bone are higher in men than in women.

Researchers found that lead levels in seminal plasma varied widely, but found a "significant association" between high lead levels and low fertilization rates. Lead levels accounted for a fifth of the variance in fertilization rates, the report said.

To fertilize an egg, a sperm must bind to it. The head of the sperm contains receptors for mannose, a type of sugar found on the outer coating of the egg. Mannose is crucial to the binding, and a mannose-induced reaction triggers the release of digestive enzymes that make it easier for the sperm to penetrate the egg.

Benoff said the study produced evidence that higher lead levels interfere with both the ability of the sperm to bind to the egg and with its ability to fertilize it.

In the 140 men whose partners were undergoing in vitro fertilization, higher lead levels in seminal plasma correlated with low expression of mannose receptors and with the mannose-induced reaction, the study found. Researchers also found that higher lead levels were associated with premature mannose-induced reaction that occurs before the sperm has reached the egg.

When healthy sperm were exposed to increasing doses of lead, the results were the same, the study found.

"These biomarkers provide relatively unambiguous endpoints for lead-induced reproductive toxicity and our data suggest that lead is acting at multiple levels in testis and sperm to decrease human male infertility," Benoff said