Taurine restores oocyte quality by enhancing mitochondrial function in mice exposed to dibutyl phthalate during...

Adolescence represents a vulnerable window for ovarian development, during which oocytes rely heavily on mitochondrial bioenergetics and redox homeostasis. Dibutyl phthalate (DBP) is a widely used plasticizer recognized for its endocrine-disrupting properties. It can compromise oocyte integrity during these sensitive developmental stages. We found that adolescent DBP exposure impairs oocyte quality in mice, causing fragmentation, meiotic arrest, spindle disorganization, and chromosome misalignment. Smart RNA-seq analysis of DBP-exposed oocytes revealed that these defects are associated with mitochondrial dysfunction, particularly impairment of respiratory chain complex I. Consistently, DBP exposure induced mitochondrial clustering, excessive ROS production, loss of membrane potential, ATP depletion, and suppression of complex I activity, which could be recapitulated by in vitro administration of MBP, a bioactive DBP metabolite. Inhibition of complex I with rotenone reduced oocyte maturation and mitochondrial membrane potential, supporting complex I as a primary target of DBP-induced injury. Mechanistically, DBP reduced 5-taurinomethyluridine (τm⁵U) modification of mitochondrial tRNAs and decreased the protein level of the mitochondrially encoded complex I subunit MT-ND1, leading to impaired complex I activity. Systemic taurine availability was also reduced. Notably, taurine supplementation restored τm⁵U modification and enhanced MT-ND1 translation, thereby rescuing complex I activity and reestablishing mitochondrial function. These improvements mitigated DNA damage and apoptosis, corrected meiotic defects, and rescued oocyte maturation, embryonic development, and fertility. Together, our findings indicate that DBP disrupts oocyte development by impairing mitochondrial redox homeostasis in mice, and suggest that taurine supplementation can restore mitochondrial function and preserve female fertility under environmental insults.