Nfkb1 loss sped up early menopause in animal models

Monash University researchers have identified a gene that may help explain early menopause and some forms of infertility. In pre-clinical animal studies, loss of Nfkb1 accelerated ovarian ageing and depleted the ovarian reserve.

Dr Karla Hutt led the study. Reproductive Biology and Endocrinology published the paper, titled Mice lacking NF-ĸB1 undergo premature ovarian ageing.

Women’s fertility declines with age because the ovaries gradually lose eggs and follicles. That loss can lead to infertility, irregular cycles and menopause.

Monash University said the causes of age-related egg and follicle loss remain poorly understood. The same gap applies to premature ovarian ageing and premature menopause.

Dr Karla Hutt study

In the animal models, females rapidly lost eggs and follicles when Nfkb1 was absent. That pattern resembled diminished ovarian reserve or early menopause in humans.

The team also found more inflammation in the ovaries after Nfkb1 loss. According to the study, chronic low-grade ovarian inflammation is a hallmark of ageing.

Dr Hutt said: “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.”

Only a small number of genetic factors linked to early and rapid egg and follicle loss have been identified to date. Because of that, the Monash University findings add a new lead for fertility genetics research.

Dr Hutt also linked premature ovarian insufficiency to wider health effects. She said lower ovarian hormone production can increase the risk of heart disease and osteoporosis.

The study found Nfkb1 is important for maintaining follicle numbers. It also supports ovarian hormone production and female reproductive longevity.

Following these pre-clinical results, Dr Hutt said the team should examine Nfkb1 in women experiencing infertility. She said such work could inform clinical care and point to new fertility genetics targets.

Monash University said the gene, or inflammatory pathways linked to it, could one day become intervention targets. Those targets could aim to extend ovarian and reproductive lifespan.