Lipotoxicity and Oocyte Quality in Mammals: Pathogenesis, Consequences, and Reversibility

Metabolic stress conditions are often characterized by upregulated lipolysis and subsequently increased serum free fatty acid (FFA) concentrations, leading to the uptake of FFAs by non-adipose tissues and impairment of their function. This phenomenon is known as lipotoxicity. The increased serum FFA concentrations are reflected in the ovarian follicular fluid, which can have harmful effects on oocyte development. Several studies using in vitro and in vivo mammalian models showed that altered oocyte metabolism, increased oxidative stress, and mitochondrial dysfunction are crucial mechanisms underlying this detrimental impact. Ultimately, this can impair offspring health through the persistence of defective mitochondria in the embryo, hampering epigenetic reprogramming and early development. In vitro and in vivo treatments to enhance oocyte mitochondrial function are increasingly being developed. This can help to improve pregnancy rates and safeguard offspring health in metabolically compromised individuals.