Effects of chlorogenic acid on gut microbiota composition and ovarian function in mice with D-galactose-induced premature ovarian failure

Premature ovarian failure (POF) refers to a disease state linked to ovarian failure caused by overdepletion of ovarian oocytes, abnormalities in sex hormone levels, and abnormalities in the gut microbiota. POF often comes with oxidative damage. However, the effect of chlorogenic acid (CGA) administration on POF has not yet been explored. The current study evaluated improvements in ovarian dysfunction, ovarian oxidative stress, ovarian apoptosis, and the gut microbiota in mice with D-galactose (D-gal)-induced POF that were subsequently treated with CGA. CGA treatment significantly promoted follicle development and decreased the ratio of apoptotic granulosa cells in antral follicles of POF mice. CGA treatment also restored the irregular oestrous cycle and serum hormone levels, and attenuated ovarian oxidative stress injury by increasing the expression of correlated proteins (p-Akt, Nrf2, and HO-1) in POF mice. 16S rDNA sequencing revealed significant alterations in the gut microbiota structure and abundance between the control and POF groups, and most of these alterations were reduced after CGA intervention. Spearman's correlation coefficient analysis exhibited that the regulatory effect of CGA treatment on POF-related parameters was closely connected with the abundances of Allobaculum, Blautia_A, Ileibacterium, CGA_873, UBA636, Robinsoniella, Escherichia, Enterobacterales_A, and Enterobacteriaceae_A in the gut microbiota. In conclusion, CGA intervention represents a promising therapeutic approach for POF, providing valuable insights for its application in treating female POF.