Science/Tech

DNA Repair Gene BRCA1 Helps Keep Egg Cells Young, May Extend Reproductive Lifespan

BRCA1
Repair molecules produced by functional BRCA1 "breast cancer gene" also keep egg cells from self-destructing. topnews.in

New research suggests that bolstering DNA repair systems in the ovaries could lead to new options for improving and prolonging fertility.

The key discovery of the recent study, funded by the National Institutes of Health, is that as women age, their egg cells die off because DNA damage accrues as their DNA repair systems wear out. This insight offers a new theory for why a woman's fertility declines after her mid-thirties.

One of the DNA repair genes, BRCA1, has long been associated with breast cancer. Now, defects in BRCA1 are understood to cause early menopause as well.

"We all know that a woman's fertility declines in her 40s," said Susan Taymans of the Fertility and Infertility Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute that funded the study. "This study provides a molecular explanation for why that happens. Eventually, such insights might help us find ways to improve and extend a woman's reproductive life."

The time period during which a woman is fertile is limited by the number of oocytes, or egg cells. Women are born with a set number of egg cells, or "primordial follicle oocytes." 

Over time, about 500 of those eggs are released during ovulation, and the remaining 99.9 percent are eliminated by the woman's body. The mechanism for that elimination is cellular suicide, a normal process that prevents the inheritance of damaged cells.

The cells self-destruct because they have taken a kind of DNA damage called "double-strand breaks," according to the scientists who worked on the study. As oocytes age, they accumulate more double-strand breaks. What's more, they are less able to fix those DNA breaks because their supply of repair molecules has begun to deplete.

The study looked at oocytes in mice, as well as in women ages 24 to 41. The researchers found that the activity of four DNA repair genes declined with age, those genes being BRCA1, MRE11, Rad51, and ATM. When researchers turned off those genes, they found that oocytes had more DNA breaks and higher death rates than cells with properly functioning DNA repair systems.

The research grew out of previous investigations of BRCA1, which has been heavily studied for the last 20 years because of its role in breast cancer. A defective BRCA1 gene dramatically increases a woman's risk of breast cancer.

The research confirmed that a fully functional BRCA1 gene is extremely important to women's health. Mice with non-functional BRCA1 genes were less fertile, had fewer oocytes, and had more double-stranded DNA breaks.

Damaged BRCA1 genes cause the same problems in humans, researchers say.

The study points to new therapies for improving or prolonging fertility. By understanding the molecular mechanism behind oocyte repair, scientists may someday be able to improve or prolong fertility.

The study was published in Science Translational Medicine.

 

Source: Titus S, et al. Impairment of BRCA1-Related DNA Double-Strand Break Repair Leads to Ovarian Aging in Mice and Humans. Science Translational Medicine. 2013.

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