Fertility Researchers Discover New Gene Essential for Female Fertility

Fertility researchers at the National Institute of Child Health and Human Development (NICHD) have found that a gene in female mice is essential for their egg cells to later develop beyond the two-cell stage after fertilization. This finding could lead to new insights into the causes of unexplained infertility in women. The finding may also provide an important lead for developmental biologists studying how an organism progresses from a single cell to a complex organism.

Zhi-Bin Tong, M.D, and his colleagues at NICHD's Developmental Endocrinology Branch published their findings in the November issue of Nature Genetics. The researchers reported the discovery of the gene itself in a previous paper. In the current study, the researchers reported on the function of the gene--showing that female mice must have the gene to enable their early embryos to develop normally. This is the first report in mammals that a substance produced by the mother controls the development of her offspring. The gene is called Mater (pronounced mah-ter), short for "maternal effect" gene.

"It is remarkable that such a fundamental secret of nature was uncovered as a direct result of clinical research into the causes of infertility," said Duane Alexander, M.D., Director of the NICHD. "The discovery opens up promising new areas not just in developmental biology, but in the search for causes of unexplained infertility."

The researchers have been studying premature ovarian failure, a condition that causes infertility and hormone deficiency in otherwise healthy young women, according to the leader of the research team and the study's senior author, Lawrence Nelson, M.D., of NICHD's Developmental Endocrinology Branch. Premature ovarian failure is a condition that causes infertility and hormone deficiency in otherwise healthy young women. The discovery was a byproduct of research into the origin of autoimmune premature ovarian failure in mice. These mice destroy their own ovaries by sending out an immune attack against them. The product of the Mater gene is the target of the immune attack.

To determine the function of the protein the Mater gene codes for, the researchers developed a strain of mice that lacked both copies of the gene. The researchers developed the mice using "knockout" technology, which allows them to eliminate genes from an organism. According to Dr. Nelson, the resulting female mice develop normally, yet are infertile. In the Nature Genetics paper, the researchers reported breeding the mice with genetically normal male mice. As expected, the resulting fertilized eggs divided to form two cells. However, Dr. Nelson said, instead of progressing to the three-and-four cell stage, the embryos lacking Mater remained at the two-cell stage. Male mice lacking the Mater gene were able to reproduce normally, as were female mice having only a single copy of the Mater gene.

"Our results demonstrate that Mater is a novel maternal effect gene required for embryonic development beyond the 2-cell stage in mice," the researchers wrote. The investigators are working to identify a similar gene in humans, which, if abnormal, might be a cause of unexplained infertility in women.


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