The University of Maryland School of Medicine in Baltimore has received a five-year, $6.5 million grant from the National Institutes of Health to investigate the causes of infertility. The grant will fund research conducted by the University of Maryland's Specialized Cooperative Centers Program in Reproductive Research, one of only 13 such programs in the country.
"Infertility is caused by a wide range of environmental and biological factors we don't fully understand," says Eugene D. Albrecht, Ph.D., professor of Obstetrics, Gynecology, and Reproductive Sciences at the University of Maryland School of Medicine, and director of the center. "Understanding the causes of infertility will provide clues to future treatments."
Dr. Albrecht conducted a recent study in collaboration with the Eastern Virginia Medical School in Norfolk, which found that estrogen deprivation during pregnancy could significantly impact the fertility of female offspring. "If you suppress estrogen during pregnancy, female baboons are born with only half of the normal number of eggs, and many of those eggs are unhealthy," says Gerald J. Pepe, professor and chairman, Department of Physiological Sciences at the Eastern Virginia Medical School. "When the mother's estrogen is restored before birth, the number of eggs in the offspring return to normal," says Dr. Pepe, the primary investigator for the study, published in the journal Endocrinology.
In the study, researchers used an inhibitor to disrupt an enzyme in the placenta responsible for stimulating estrogen production. Researchers then counted the egg cells produced by the female offspring. Not only were there about half the normal number of egg cells, the cells that remained were malformed. "In these abnormal eggs, the cells were not intact and there were vacuoles or bubbles inside the eggs," says Dr. Albrecht, a co-investigator for the published study. "These unhealthy cells are destined to die."
Estrogen is crucial for the development of microvilli, microscopic hair-like structures on the surface of the eggs which help provide nutrients to the egg cells. In estrogen-deprived offspring, the number of microvilli was also reduced by half. "Without the microvilli, a lot of these eggs will probably die off because they are not getting the support they need," says Dr. Pepe.
Most women are born with about one million egg cells, but only about 400 to 500 ever mature fully to be released by the ovaries during the menstrual cycle. The rest deteriorate over the years. Dr. Albrecht says a woman born with fewer healthy eggs may have a more difficult time becoming pregnant, and may even reach menopause sooner.
In addition to releasing mature eggs, a woman's ovaries produce estrogen, which are hormones responsible for regulating sexual and reproductive development. The researchers are studying the role of estrogen in fertility for both women and men, and this new NIH grant will support this continued research.
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