Regulatory mechanisms and application prospects of lipid metabolites in ovarian vitrification-induced cryoinjury.

Abstract

Ovarian vitrification is a core technology for female fertility preservation, ovarian function protection before chemoradiotherapy in cancer patients, and germplasm conservation in rare animals. Compared with slow freezing, vitrification is widely adopted for producing fewer ice crystals, causing less cryoinjury, and being operationally efficient. However, cold stress, abrupt osmotic shifts, and excessive oxidative stress during vitrification still induce ovarian cell apoptosis, plasma membrane disruption, and mitochondrial dysfunction, markedly reducing post-thaw survival and function. Lipids are essential structural components of ovarian tissue, oocyte plasma membranes, and organelle membranes; lipid metabolic homeostasis directly determines cellular cryotolerance and post-thaw developmental potential. Recent lipidomics studies have demonstrated that lipid metabolites such as fatty acids, cholesterol, sphingolipids, and carnitine alleviate ovarian vitrification-induced injury and improve cryopreservation outcomes by regulating membrane stability, oxidative stress, mitochondrial function, and follicular apoptotic signaling pathways. This review summarizes the mechanisms of lipid metabolism in mediating ovarian vitrification-induced cryoinjury, the regulatory roles of major lipid metabolites, key pre-freezing intervention strategies targeting ovarian lipid metabolism, current technological bottlenecks, and future prospects of lipid-targeted regulation in ovarian cryopreservation and fertility preservation. The aim is to provide a theoretical basis and technical reference for optimizing vitrification systems and improving thawed ovarian tissue quality.