Saturday, March 5, 2011

Low Sperm Counts Linked to Fetal Effects

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.”

By: Janet Raloff

Alpha wave may affect sleep quality

Making waves isn’t conducive to staying asleep, at least when the waves are a type of brain signal associated with being awake.

A type of brain activity known as an alpha wave emanates from the back of the head when a person is awake but relaxing with eyes closed. Scientists used to think that the wave was subdued and disappeared as a person fell deeper and deeper into sleep.

But the alpha wave doesn’t disappear; it just goes undercover during sleep, researchers report online March 3 in PLoS One. The covert alpha wave may help determine how deeply people sleep and how much noise is needed to rouse a sleeper.

The finding “stresses that sleep is really a dynamic process,” says Mathias Basner, a sleep researcher at the University of Pennsylvania in Philadelphia who was not involved in the study. The study shows that sleep doesn’t happen just in discrete blocks, as most charts of sleep stages would indicate. Instead, brain activity changes from moment to moment during sleep. 

“It may suggest that something is going on in the central nervous system that we don’t know about and should maybe pay more attention to,” Basner says. 

Scientists hadn’t ignored alpha waves on purpose, says study coauthor Scott McKinney, a sleep scientist at Massachusetts General Hospital and Harvard University. Researchers typically measure brain activity during sleep with electroencephalographs, or EEGs, devices that use electrodes on the scalp to detect electrical activity in the brain. The squiggly lines recorded by the EEG can be hard to interpret with the naked eye, so McKinney and his colleagues used computer programs to break the EEG signals from 13 volunteers down into discrete waves. The analysis revealed that alpha waves never truly go away; they just get drowned out by more vigorous signals the way spreading ripples from a small rock dropped in a pond are swamped by waves from a passing speedboat. 

Alpha wave activity decreases as people enter ever-deeper levels of sleep and increases as people cycle back into more shallow sleep stages. In study participants, the ups and downs of alpha wave activity were closely associated with how easily a person could be awoken by traffic noises, loud talking or other sounds that might be encountered in hospital or at home in a city. When alpha wave activity spiked just before a noise was played, volunteers woke up more easily than when alpha wave activity was low, the researchers found. 

Alpha wave activity may be the brain’s way of keeping people aware of their surroundings during sleep, speculates Phyllis Zee, director of the Sleep Disorders Program at Northwestern University in Chicago. Such awareness enables people to wake quickly in case of danger, but too much alpha activity might also have a downside if it prevents a good night of sleep. 

People with insomnia commonly complain that they are very light sleepers and are always aware of their surroundings, Zee says. Although many insomniacs get a full night of sleep, they report that their sleep is not restful. But laboratory tests often don’t show any abnormalities.

“The classical way we’re scoring sleep may not give a good handle on what a patient really experiences,” she says. “This new way of analyzing depth of sleep may be used to get a better understanding of a patient’s complaint.”

By: Tina Hesman Saey