Writing in the journal PLoS One, researchers from the University of Southern California suggest that exposure to chemicals as a fetus may lead to changes in sperm DNA that can cause infertility. In the US, about 4 million married couples of child-bearing age are infertile and in approximately 40 percent of the cases, the infertile partner is the man. In most cases, the cause of the male infertility is not known. The new study suggests that epigenetics, or the way DNA is processed and expressed, may be the underlying cause for male infertility.
Epigenetic change, which is defined as in addition to changes in genetic sequence, includes any process that alters gene activity without changing the DNA sequence. Some of these epigenetic changes are inherited from one generation to the next.
The study was based on semen samples from male members of couples attending an infertility clinic. Using molecular biology techniques, the researchers studied the epigenetic state of DNA from each man's sperm. They found that sperm DNA from men with low sperm counts or abnormal sperm had high levels of methylation, which is one of the ways the body regulates gene expression. However, DNA from normal sperm samples showed no abnormalities of methylation.
"This is the first report based on our knowledge that a broad epigenetic defect is associated with abnormal semen development," said researcher Rebecca Sokol. "From our data, it is plausible to speculate that male infertility may be added to the growing list of adulthood diseases that have resulted from fetal origins."
DNA methylation results from well known biochemical alterations that occur during epigenetic reprogramming, which is a normal physiologic process that occurs during embryonic development. "Disturbance of epigenetic programming can result in abnormal gene activity or function, even if there is no change in DNA sequence," explained Sokol.
The epigenetic irregularity found in the abnormal sperm samples suggests that the underlying mechanism for these epigenetic changes may be improper erasure of DNA methylation during epigenetic reprogramming of the male germ line.
"If we can identify what causes these changes to the sperm DNA, then we might be able to prevent certain types of male infertility," concluded Sokol. "This is particularly important because recent animal studies have suggested that epigenetics may have broader implications. Exposures to chemicals as a fetus may lead to adult diseases. Perhaps such exposures may be causing the changes in the sperm DNA that we have identified."
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Source: University of Southern California
