Estrogen is vital to male fertility -- specifically to sperm count. That discovery, coupled with the debate over declining sperm counts worldwide, means "we must be concerned about the potential for environmental chemicals to influence male reproductive function," said Rex A. Hess, a professor of veterinary biosciences at the University of Illinois and principal author of the Nature report.
"If there is a normal function for estrogen in the male, and that function is required for normal fertility, then it is logical to hypothesize that chemicals that interfere with estrogen receptors may interfere with fertility," Hess said. "Until now, there has been no known function for estrogen in the male. We have had nothing to focus on. Now we can ask the question: Does this chemical or that chemical interfere?"
Potential environmental influence on fertility, such as exposure to pesticides and industrial chemicals, has sparked controversy since 1992, when Copenhagen University researchers concluded that sperm counts were declining around the world. In late November, a team led by Shanna Swan of the California Department of Public Health reached a similar conclusion after reconsidering the data from the 61 studies used in the Copenhagen findings.
The Nature paper focuses on the regulatory role of estrogen-induced fluid reabsorption during the transfer of sperm in fluid from the testis through the efferent ductules -- a series of small tubes that act like kidneys, producing concentrated semen instead of urine -- to the epididymis, where sperm mature and are stored.
"We have found that estrogen regulates fluid reabsorption in the efferent ductules of the male," Hess said. "It is important for the uptake of water, ions and proteins from the fluid that carries the sperm. The efferent ductules are responsible for reabsorbing nearly 90 percent of the water from this fluid. Without the reabsorption, the sperm remain diluted and therefore incapable of normal maturation in the epididymis."
The paper is part of three collaborative studies done over seven years on male estrogen -- funded in part by the U.S. Department of Agriculture and the U. of I.-- by a team that includes Janice Bahr, a professor of physiology, molecular biologist David Bunick and Hess.
In another study, published in the December issue of the Journal of Adrology, the researchers report that the number of genes that express estrogen receptors in the efferent ductules of rats -- when operating normally -- is 3.5 times greater than the estrogen receptor message in the female reproductive tract.
"This means you have a target for estrogen, and there are plenty of targets for the estrogen to bind to," Hess said. "It was surprising to find the protein in such a high concentration. We knew it would be there, but finding so much was unexpected."
The Nature findings resulted from studies of estrogen function in the reproductive tracts of mice, including genetically produced mice whose estrogen receptors are non-functional. As in humans, the mice used in the research had similarities in their estrogen, estrogen receptors and efferent ductules.
Hess, Bahr and Bunick reported in the 1994 Proceedings of the Estrogens in the Environment, that they had found a new source of potential estrogen synthesis in males, in the germ cells of the testis and sperm in the epididymis of mice, rats and chickens. Similar findings have been made in black bears.
When estrogen receptors are knocked out, the fluid "accumulates at the site of production " just as happens when you get a blocked waste pipe and run the tap," writes Richard M. Sharpe of the Medical Research Council Reproductive Biology Unit in Edinburgh, Scotland, in an accompanying "News and Views" article on Hess' findings. "This build-up progressively impairs sperm production because of the increased fluid pressure within the testis."
In 1993, Sharpe theorized that declines in sperm counts might be occurring because of a complex interference with hormones involving the hypothalamus in the brain and the pituitary gland during development of the testis.
Now that the research has provided the first recognized physiological function for estrogen in males, Hess said, the next step in the research is to determine the biochemical action. "We have known that estrogen is present in the male, and in high concentrations in the seminal fluids, but we did not know why it was there," he said. "Now we can focus on the function of fluid reabsorption and on what genes are regulated by the estrogen."
"Estrogen is not only important in the female for fertility, but it also exerts its influence on the male, from birth to death," Hess said. "We can now say that this female hormone is intimately involved in regulating fertility in the male, because if you block the estrogen receptor's function as we've shown here, you will have infertility. It is very likely that this will be a similar finding in humans."
Coauthors of the Nature paper are Hess, Bunick and Bahr, along with Ki-Ho Lee of the U. of I. department of veterinary biosciences; Julia A. Taylor and Dennis B. Lubahn of the departments of biochemistry and child health at the University of Missouri at Columbia; and Kenneth S. Korach of the National Institutes of Health National Institute of Environmental Health Sciences at Research Triangle Park, N.C.
Coauthors of the paper in the Journal of Andrology are Hess, Bunick, Lubahn, Bahr, Daniel H. Gist of the department of biological sciences at the University of Cincinnati, Amy Farrell and Paul S. Cooke of the U. of I. department of veterinary biosciences, and Geoffrey L. Greene of the Ben May Institute for Cancer Research at the University of Chicago.