Spermidine ameliorates homosalate-induced mouse oocyte defects via regulation of mitochondria and cytoskeleton.

Abstract

Homosalate (HMS) is an organic ultraviolet filter widely used in personal care products. Although its endocrine-disrupting properties are recognized, its impact on oocytes remains poorly characterized. Through network pharmacology, Smart-seq2 sequencing, and in vitro models, our findings indicate that HMS exposure delayed meiotic progression at metaphase I (MI) in mouse oocytes. HMS treatment led to persistent oxidative stress, DNA damage, and early apoptosis. It also impaired mitochondrial function. Treated oocytes exhibited decreased membrane potential (ΔΨm), reduced ATP production, and downregulation of oxidative phosphorylation genes (Nd2, Nd4, Cytb, and Cox1). Alongside this bioenergetic deficit, we observed disrupted cytoskeletal dynamics, characterized by aberrant spindle morphology, compromised F-actin assembly, and destabilized kinetochore-microtubule (K-MT) attachments, which contribute to aneuploidy. Supplementation with spermidine (SPD) mitigated these deleterious effects by maintaining mitochondrial function and cytoskeletal stability. These findings provide mechanistic insights into the reproductive toxicity of HMS in oocytes and highlight SPD as a potential protective intervention against such environmental stressors.