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Fertility researchers at the National Institute of Child Health and Human Development (NICHD) have discovered a gene present in the human egg that may be essential for early embryo development.
The gene may also play a role in premature ovarian failure, a mysterious condition in which the ovaries stop functioning years, and sometimes decades, before natural menopause.
"This finding could lead to new insights into the causes of unexplained infertility in women," said Duane Alexander, M.D., Director of the NICHD. The finding may also lead to a better understanding of the possible role that the immune system may play in some cases of premature ovarian failure."
Zhi-Bin Tong, M.D., and his colleagues at NICHD's Developmental Endocrinology Branch published their findings in the April issue of "Human Reproduction". Their discovery builds upon past research conducted with mice. In previous work, the researchers discovered a gene found in female mice, which they called "Mater", short for "maternal effect" gene. The mouse "Mater" gene produces a protein that is essential for a fertilized egg to develop. Female mice lacking the gene produce eggs that cannot survive beyond the two-cell stage after fertilization. In the current study, the researchers identified a gene in women that appears to be the human counterpart to the mouse "Mater" gene. "The identification of a human "Mater" gene that is similar to the "Mater" gene found in mice is an important discovery," said Lawrence Nelson, M.D., the senior author of the study and a member of NICHD's Developmental Endocrinology Branch. "If the human gene is found to serve the same function as the mouse gene, it may result in a new approach to the study and treatment of female infertility." The researchers discovered the mouse gene as part of their attempt to better understand premature ovarian failure. In this condition, the ovaries stop functioning prematurely, sometimes long before the age of 40. The researchers have found that in some cases of this disorder, the immune systems of otherwise healthy young women appear to attack and destroy their ovaries. Mice that have a disorder resembling premature ovarian failure experience such an immune attack on the ovaries. The researchers found that the protein produced by the mouse "Mater" gene appears to be the target of the immune system attack. To determine the function of this protein, the researchers developed a strain of mice that lacked both copies of the gene and discovered that the females were infertile.
According to Dr. Nelson, the researchers discovered that the DNA of human and mouse "Mater" genes are 67 percent identical. They also found that the proteins produced by the human and mouse "Mater" genes are 53 percent alike and share a number of similar features. "These structural similarities between species suggest that the protein produced by the "Mater" gene may have a similar function in the mouse and human," the researchers wrote. “We propose that a similar human "Mater" mutation or its protein deficiency may cause infertility in some women." The researchers next plan to investigate whether the human form of "Mater" is the target of the immune attack in women who have premature ovarian failure. They also plan to examine women who have a history of successful fertilization, but whose embryos are unable to develop, to try to find mutations of the human "Mater" gene that could make their eggs incapable of developing beyond the two-cell stage. If they discover that such a deficiency exists, it is possible that researchers may one day be able to induce pregnancy by injecting human "Mater" protein into the egg cells of these women before conception. NATIONAL INSTITUTES OF HEALTH
National Institute of Child Health and Human Development Contact: Susan Marsiglia Robert Bock (301) 496-5133 The NICHD is part of the National Institutes of Health, the biomedical research arm of the federal government. The Institute sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD publications, as well as information about the Institute, are available from the NICHD Web site http://www.nichd.nih.gov,
or from the NICHD Clearinghouse,1-800-370-2943;
e-mail: NICHDClearinghouse@mail.nih.gov.
Message posted by: Trevor M. D'Souza
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