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Premature Ovarian Failure Results From Egg-Specific Gene Mutations

February 3, 2009

As many as 1 percent of women suffer premature ovarian failure, a disorder associated with infertility that has important health implications as well.

Now, researchers at Baylor College of Medicine and Shandong University in China find that a mutation in a gene called FIGLA causes early ovarian failure in a percentage of women. A report of their work appears in the American Journal of Human Genetics.

“We hope to use the information from this study and others that identify genes associated with this problem to find biomarkers in blood that can help us determine a woman’s risk of early infertility,” said Aleksandar Rajkovic, M.D., Ph.D., associate professor of obstetrics and gynecology at BCM and senior author of the paper.

Premature ovarian failure

“It affects 1 percent of women,” he said. “While most people associate it with infertility, women with premature ovarian failure face an increased risk of cardiovascular disease, osteoporosis and premature death. Ovarian reserves are important for women’s health.”

In looking for genes that cause the disorder, Rajkovic and his colleagues here and in China concentrated on those that are most likely to function in the ovary. A gene mutation does not totally halt gene activity, but Rajkovic believes it can accelerate the loss of eggs (or germ cells). When all the eggs are lost, the ovaries stop producing estrogen, leading to menopause symptoms.

Mutations

In this study, Rajkovic and his collaborators screened 100 Chinese women with premature ovarian failure for mutations in FIGLA and found three different kinds of mutations in the FIGLA genes of four. FIGLA is one of four transcription factors found to control the differentiation of egg cells early in development. Transcription factors govern the activity of genes, turning them off and on and modulating the extent to which they are active.

Other genes involved

The other genes involved include NOBOX, GDF9 and BMP 15, said Rajkovic. Mutations in these can lead to premature ovarian failure as well, he said. “We hope to define the majority of the genes that are part of the cellular pathways involved in ovarian failure,” said Rajkovic. “Ideally in the future we will offer a test to women to look at all the genes involved in premature ovarian failure.”

Risk of disorder

He anticipates that a gene chip would be helpful in such diagnosis, which can help in counseling women or their children about the risk of early ovarian failure.

Others who took part in this work include Youngsok Choi of BCM, Han Zhao of BCM and the Center for Reproductive Medicine at Shandong Provincial Hospital and Shandong University, Zi-Jiang Chen, Yingying Qin, Yuhua Shi and Shan Wang of Shandong and Joe Leigh Simpson of Florida International University College of Medicine in Miami.

Funding for this work came from the National Institutes of Health, the March of Dimes, the National Natural Science Foundation of the People’s Republic of China and the National Basic Research Program of China.

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