Dehydroepiandrosterone shifts energy metabolism to increase mitochondrial biogenesis in female fertility with advancing age

Abstract

Female reproductive aging is an irreversible process associated with a decrease in oocyte quality, which is a limiting factor for fertility. Previous studies have shown that dehydroepiandros-terone (DHEA) has been shown to improve in vitro fertilization (IVF) outcomes in older women. Herein, we showed that the decline in oocyte quality with age is accompanied by a significant decrease in the level of bioenergetic metabolism genes. We compared the clinical characteristics between groups of infertile women who either received DHEA or did not. Treatment with DHEA may enhance oocyte quality by improving energy production and metabolic reprogramming in cumulus cells (CCs) of aging women. Our results showed that compared with the group without DHEA, the group with DHEA produced a large number of day-three (D3) embryos, top-quality D3 embryos, and had improved ongoing pregnancy rate and clinical pregnancy rate. This may be because DHEA enhances the transport of oxidative phosphorylation and increases mitochondrial oxygen consumption in CCs, converting anaerobic to aerobic metabolism commonly used by aging cells to delay oocyte aging. In conclusion, our results suggest that the benefit of DHEA supplementation on IVF outcomes in aging cells is significant and that this effect may be mediated in part through the reprogramming of metabolic pathways and conversion of anaerobic to aerobic respiration.