Low sperm counts linked to fetal effects

Male infertility may stem from in utero chemical exposures

Scientists report being able to take the measure of a man — or at least his ability to father children — with a $40 pair of measuring calipers. They use the instrument to carefully assay the distance between his genitals and anus.

In a new study, this distance proved a potent predictor not only of sperm count but also of semen quality — the concentration of sperm as well as sperm motility and shape. Of these, sperm count correlated best with anogenital distance, or AGD. In fact, “AGD is now the strongest predictor of sperm count that we know of,” says Shanna Swan, a reproductive epidemiologist in the University of Rochester’s Department of Obstetrics and Gynecology.

No one knows what triggered the reproductive changes for which AGD serves as a marker, Swan says. A number of environmental factors — including a mother’s smoking or obesity — appear able to perturb fetal androgen levels. But in 2005, Swan’s group correlated a diminished AGD in infant boys with a small penis — and both appeared linked to elevated concentrations of chemicals known as phthalates in urine collected from the boys’ mothers during prenatal visits. Phthalates constitute a widely used family of chemicals that serve as solvents and that make certain plastics flexible. Studies show people throughout the industrial world are regularly exposed to them.

The share of reproductively challenged men that Swan’s team turned up in the new study was large. Based on semen measurements, one in four of the 126 apparently healthy men who were tested appeared subfertile at best — and possibly infertile, Swan and her colleagues report online March 4 in Environmental Health Perspectives. The men in this group had sperm concentrations at or below 20 million per milliliter, a cutoff that Swan says doctors often use to determine whether men who haven’t been able to father a child warrant referral to a fertility clinic.

Animal studies show that AGD is controlled early in prenatal development by sex hormones, especially androgens such as testosterone, notes Richard Sharpe of Queen’s Medical Research Institute in Edinburgh. “AGD therefore offers a lifelong readout of fetal androgen exposure — and just for this critical period of vulnerability,” which he says roughly corresponds to weeks eight through 14 of human gestation.

His group linked shortened AGD in rodents with reduced sperm counts, birth defects affecting the genitals and smaller male organs. But there remained the nagging question of whether AGD provided a similarly important readout of androgen exposure in early human development.

“We now know it does,” Swan says.

The evidence emerged among residents of Rochester, N.Y., who took part in the first study of semen quality among healthy U.S. men. “These were kids in college,” Swan says. “They volunteered to be tested just because they wanted to make $75,” the compensation for participating.

Those whose anogenital distance was below the median for their build were 7.3 times as likely to be in the subfertile group as were those whose AGD was above the median, Swan says. Her team’s analyses found less than one-tenth of a percent likelihood that this association might be due to chance.

“Up until now, nobody has really understood what might be the impacts of a shortened AGD on quality of life,” says Philip Landrigan, director of the Children’s Environmental Health Center at the Mount Sinai School of Medicine in New York City. “So this observation that a short AGD is correlated with low sperm count is new stuff and, I think, very important.”

One reason: Getting useful measures of sperm is complicated because numbers fluctuate with a host of factors, including season, ambient temperature and how long a man has been abstinent. “The beauty of measuring AGD,” Landrigan says, “is that once it’s established [in the womb], it remains stable — as long as you adjust for the overall size of the man.” This gives doctors “a new way to screen men — a new tool in their quiver.”

Data since 1992 have pointed to low and falling sperm counts among men throughout much of the developed world. “And we’ve been touting for years that this may have its origins in fetal life,” Sharpe says. “But we’ve lacked the direct evidence.” The new Rochester data, he says, now offer an explanation for low sperm counts in a large share of young men.

Sharpe’s team also has shown that fetal exposure to some phthalates can shorten AGD in rats and diminish their adult sperm production. The sperm changes traced back to a reduced proliferation of Sertoli cells in the fetal testes. “Ultimately,” he says, “the number of Sertoli cells will determine how many sperm you can make in adulthood.”

Janet Raloff is the Editor, Digital of Science News Explores, a daily online magazine for middle school students. She started at Science News in 1977 as the environment and policy writer, specializing in toxicology. To her never-ending surprise, her daughter became a toxicologist.

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