Nano-encapsulated senolytics cocktail ameliorates germ cell senescence in female mice

Low-quality oocytes directly affect fertilization and embryo developmental ability, and further contributes to infertility in women. Dasatinib and quercetin, as a senolytics, has been explored extensively in various age-related diseases. Here, we report that nano-encapsulated senolytics cocktail (D+Q) efficaciously ameliorates the the quantity and quality of follicles and oocytes in vitro and in vivo. D+Q cocktail supplementation reduces the level of ROS in aged oocytes, decreases the frequency of fragmentation, maintains the spindle integrity, rescues mislocalized cortical granules, rescues mitochondrial membrane potential and alleviates DNA damage and apoptosis in vitro. Nano-encapsulated D+Q cocktail effectively ameliorates the fertility deficits in the cyclophosphamide-induced primary ovarian failure (POF) mice model. Moreover, RNA sequencing analysis shows that D+Q cocktail improves the fecundity of POF mice by increasing development gene expression and reduces the senescence-associated secretory phenotype (SASP) accumulation. Taken together, our data show that the D+Q cocktail helps to improve assisted reproductive technology and reproductive outcomes in POF.