Exogenous Putrescine Supplementation Improves Cyclophosphamide-induced Premature Ovarian Insufficiency in Mice

The incidence of premature ovarian insufficiency (POI) is gradually increasing, and currently no clinical treatments are available to restore ovarian function in POI patients, which severely affects the physical and mental health of young women with fertility needs. Putrescine is a type of polyamine found in the human body and different foods, and research has shown that adding putrescine to drinking water can reduce embryo resorption rates in aged mice. Polyamines are also closely related to apoptosis, with ovarian granulosa cells (GCs) apoptosis considered an important factor in follicular atresia, which may lead to POI. Therefore, we investigated putrescine's actions in POI. We generated a drug-induced POI mouse model by intraperitoneally injecting cyclophosphamide (Cy) into animals. Putrescine was then added to their drinking water to explore its effects on ovarian function in mice. In vitro, we added 4-hydroxycyclophosphamide (4-HC) and putrescine to a GCs line to examine the specific mechanisms underpinning putrescine actions. We discovered that putrescine improved ovarian function and fertility in Cy-induced POI mice and ameliorated GC apoptosis via P53 signaling. These findings provide potential therapeutic strategies for patients with POI.