Bushen Zhuluan Decoction alleviates diminished ovarian reserve by regulating the m⁶A modification of PLGF

Diminished ovarian reserve (DOR) is an important pathogenic factor contributing to infertility among women of childbearing age. Bushen Zhuluan Decoction (BZD) has been observed to enhance ovarian function. The aim of this study was to investigate the pharmacological effects of BZD on DOR and elucidate its underlying mechanism of action. A DOR rat model was established by gastric gavage with Tripterygium wilfordii polyglycosides (TWPs). Ovarian pathological alterations were evaluated using HE staining. The serum FSH, LH, E2 and AMH levels were measured by ELISA; the mRNA and protein expression levels were determined by qRT‒PCR, western blot analysis and immunohistochemistry; and a specific kit was used to assess the m⁶A methylation level. The findings indicated that both m6A methylation levels and METTL3 expression were significantly decreased in the ovarian tissues of DOR rats and this effect was partially reversed by BZD treatment. METTL3 knockdown decreased PLGF mRNA stability and expression in human ovarian granulosa cells in a m⁶A-dependent manner. Moreover, BZD intervention improved ovarian function in DOR rats by regulating METTL3-mediated PLGF m⁶A modification. Taken together, these findings indicate that BZD alleviated DOR by the regulation of METTL3-mediated PLGF m⁶A modification.