Putrescine Improves Oocyte Quality in Aged Mice by Modulating the IP3R-GRP75-VDAC1 Complex

Objectives Female fertility declines with age, primarily due to a decrease in both oocyte quantity and quality. While putrescine supplementation has been shown to improve oocyte quality in aged mice, the underlying mechanisms remain unclear. In particular, whether putrescine modulates mitochondrial-associated membranes (MAM) and mitigates mitochondrial calcium overload via the IP3R-GRP75-VDAC1 complex has yet to be elucidated. Materials and methods In this study, we investigated the effects of putrescine on oocyte quality using three groups: eight-week-old mice (Young), 40-week-old mice (Old), and 40-week-old mice with 0.5 mM putrescine supplementation during in vitro maturation (Put). Key parameters assessed included oocyte mass, MAM number, mitochondrial calcium levels, mitochondrial function, and apoptosis. Results Aged mice exhibited significantly lower anti-Müllerian hormone (AMH) levels and a reduced oocyte count, accompanied by a decline in oocyte quality. Putrescine supplementation significantly improved first polar body extrusion and blastocyst formation rates in aged oocytes. Additionally, it reduced MAM formation and weakened IP3R-GRP75-VDAC1 interactions, alleviating mitochondrial calcium overload. Consequently, mitochondrial function was enhanced, ATP production increased, and apoptosis reduced. Conclusion Putrescine ameliorates the quality of aged oocytes by modulating Ca ²⁺ transfer at MAM. These findings provide novel insights into the role of putrescine in improving oocyte quality and suggest its potential as an in vitro maturation (IVM) supplement to enhance reproductive outcomes in older women by modulating MAM.