Researchers at Monash University say they have found a gene in animal models that could help explain why some women experience early loss of fertility and premature menopause.
Fertility in women falls sharply with age as eggs and ovarian follicles are gradually lost, but the biological reasons for that decline and for conditions that cause it to occur prematurely have largely remained a mystery.
In preclinical studies led by Dr Karla Hutt and published in the Journal of Reproductive Biology and Endocrinology, the team identified the gene Nfkb1 as a potential protector of female reproductive lifespan. Animals missing Nfkb1 showed rapid depletion of their ovarian reserve, producing a model that resembles diminished ovarian reserve or early menopause in humans.
The loss of Nfkb1 was linked with increased inflammation in the ovaries. “Our findings suggest that loss of the Nfkb1 may cause chronic low-grade inflammation in the ovary, accelerating the age-associated depletion of follicles, leading to early loss of fertility and premature menopause,” Dr Hutt said.
Only a handful of genetic factors tied to rapid egg and follicle loss have been discovered so far, making this result notable. “Women with premature ovarian insufficiency not only experience infertility, but also undergo an early decline in ovarian hormone production. This can increase the risk of long-term health conditions such as heart disease and osteoporosis,” Dr Hutt said. “This gene is clearly important for maintaining follicle numbers, and thus ovarian hormone production and female reproductive longevity.”
Dr Hutt urged investigation of Nfkb1 in women facing infertility, saying such studies “could provide valuable insights into fertility genetics which could help inform clinical care.” She added that the gene or related inflammatory pathways “could become targets for interventions aimed at extending a woman’s ovarian and reproductive lifespan.”
