Abstract

Ethnopharmacological relevance Lycium barbarum L. (goji berry), a traditional medicinal and edible herb, has long been employed for its anti-aging, vision-enhancing, and anti-inflammatory properties. Lycium barbarum glycopeptide (LbGP), a major bioactive glycoconjugate isolated from this plant, possesses documented antioxidant and immunomodulatory activities. However, its specific therapeutic efficacy in counteracting reproductive aging and the precise mechanisms underlying its protective effects on oocyte quality remain to be fully elucidated. Aim of the study To investigate the restorative effects of LbGP on ovarian function and oocyte quality in aged mice and to decipher the underlying mechanisms involving both oocyte-intrinsic metabolic regulation and extrinsic ovarian microenvironment remodeling. Materials and methods A reproductive aging model was established using naturally aged female mice supplemented with LbGP. Follicular development and oocyte quality were assessed via histological analysis, in vitro fertilization (IVF), and early embryonic culture. Mitochondrial function and oxidative stress levels were monitored using live-cell imaging. Mechanistic insights were generated through integrated proteomic analysis of oocytes and single-cell RNA sequencing (scRNA-seq) of ovarian tissues to identify key metabolic pathways and cellular composition changes. Results LbGP supplementation significantly promoted follicular development, enhanced oocyte maturation competence, and improved subsequent early embryonic potential compared to untreated aged mice. Mechanistically, proteomic analysis revealed that LbGP restored mitochondrial function in aged oocytes by activating PPAR signaling pathways, leading to reduced intracellular reactive oxygen species (ROS) accumulation and DNA damage. Furthermore, ovarian single-cell transcriptomics demonstrated that LbGP systemically remodeled the aged ovarian microenvironment by increasing functional granulosa cell populations