Identification of curcumin as a novel potential drug for promoting the development of small ovarian follicles for infertility treatment

In-vitro fertilization is an effective treatment for various causes of infertility. However, management of women with poor ovarian response or premature ovarian insufficiency remains challenging because these women have underdeveloped small ovarian follicles that do not respond to hormone treatment. In-vitro activation of small follicles has been developed but its efficiency has much room for improvement. In the current study, we provide several lines of evidence showing that curcumin, an FDA-approved traditional medicine, can specifically promote the development of mouse ovarian follicles from the primary to secondary stage, which greatly potentiates these small follicles for subsequent in-vivo development into antral follicles that can be ovulated. Mechanistically, we show that curcumin promotes the proliferation and differentiation of granulosa cells and the growth of oocytes by activating the phosphatidylinositol 3 kinase (PI3K) signaling pathway. Most importantly, we show that in-vitro treatment of human ovarian tissues with curcumin can promote the in-vivo survival and development of small human ovarian follicles, showing that curcumin can be used as a potential drug to increase the success rate of in-vitro activation of small human follicles. We thus identify curcumin as a novel potential drug for promoting the development of small human ovarian follicles for infertility treatment.