A new study in women undergoing fertility procedures shows that eggs in a woman’s ovaries lose the ability to repair DNA double-strand breaks with age. The findings may help explain why women rapidly lose eggs and reproductive capacity with age. Kutluk Oktay and colleagues found that knocking down genes involved in double-strand break repair in mice depletes the number of eggs in the ovaries. Specifically, the proteins responsible for patching up DNA damage in egg cells work less efficiently with age. In instances where DNA damage cannot be repaired, eggs cells may choose death through a cell suicide mechanism. Eggs unable to repair double-strand breaks are also less likely to be fertilized, which may explain why fertility declines with age.
Some DNA-damaged eggs may result in pregnancies, but developing fetuses may be more susceptible to chromosomal abnormalities. (The same genes and molecules that play a role in fixing DNA damage may also play a role in making sure chromosomes are stable.) One of these genes isBRCA1, widely known as the breast cancer gene. Previous work has found that women with BRCA1 mutations produce fewer eggs in response to fertility drugs compared with women lacking the mutation. Here, Oktay and colleagues assessed fertility in a group of 80 women who were tested forBRCA1 mutations. By measuring a hormone called anti-Müllerian hormone in blood samples, the researchers were able to estimate how many eggs a woman has left in her ovaries. They found that women with BRCA1mutations had a lower ovarian reserve than women without the mutation. The results suggest that the BRCA1 gene and other DNA repair genes may contribute to decreased fertility in aging women. The authors argue that these findings may eventually lead to treatments that can delay reproductive aging. A related Focus article discusses the findings.
Article: "Impairment of BRCA1-Related DNA Double-Strand Break Repair Leads to Ovarian Aging in Mice and Human," by S. Titus; F. Li; R. Stobezki; K. Akula; E. Unsal; K. Jeong; F. Moy; S. Goswami; K. Oktay at New York Medical College in Rye, NY; S. Titus; F. Li; R. Stobezki; K. Akula; E. Unsal; K. Jeong; F. Moy; S. Goswami; K. Oktay at New York Medical College in Valhalla, NY; E. Unsal at Istanbul Bilim University School of Medicine in Ankara, Turkey; M. Dickler; M. Robson at Memorial Sloan-Kettering Cancer Center in New York, NY; M. Dickler; M. Robson at Weill Medical College of Cornell University in New York, NY; S. Goswami at Yeshiva University in New York, NY; K. Oktay at Reproductive Specialists of New York in Rye, NY.