Overexpression of constitutively active protein FOXO3 may increase ovarian reproductive capacity in ageing mice reports a paper published in Nature Communications this week. The work highlights that naturally occurring Foxo3 may be a relevant avenue for research into potential interventions to alleviate physiological decline of female fertility.

The numbers of primordial follicles in the ovaries decrease with age in female mice, as in humans, as follicles are recruited for ovulation. Emanuele Pelosi and colleagues find that transgenic expression of an active form of the protein FOXO3 increases the number of ovarian follicles and therefore enhances fertility in aging female mice. They report that fertility in these transgenic females is increased by 31-49%. In addition, the gene expression profiles of these ovaries are similar to those of ovaries from younger mice that do not express the transgene.

This work emphasizes the role of Foxo3 as a guardian of the ovarian follicle reserve in mice and also as a potential determinant of the onset of menopause.