Dicyclohexyl phthalate exposure impairs early embryonic development and disrupts offspring reproductive function via oxidative stress-mediated mitophagy.
Dicyclohexyl phthalate (DCHP) is a widely detected environmental endocrine-disrupting chemical found in various consumer products. Maternal exposure to DCHP may adversely affect offspring health. However, its effects on early embryonic development and female offspring, and the underlying mechanisms affecting offspring reproductive function remain unclear. In this study, using an in vitro mouse embryo culture system and a maternal gestational exposure model, we found that DCHP exposure induced DNA damage, disrupted spindle morphology and chromosome alignment during the first cleavage of early mouse embryos, accompanied by reduced blastocyst formation. Transcriptomic analysis of ovarian tissues from high-dose DCHP-exposed offspring revealed enrichment of pathways related to mitochondrial dysfunction and apoptosis. Functional validation showed that DCHP exposure was associated with oxidative stress and mitochondrial dysfunction, characterized by increased reactive oxygen species levels and reduced mitochondrial membrane potential, along with increased autophagy and apoptosis. Rescue assays using Mito-TEMPO and Mdivi-1 alleviated DCHP-induced mitochondrial damage and restored blastocyst developmental competence, suggesting that mitochondrial dysfunction and subsequent mitophagy activation act as key upstream events in DCHP-induced embryonic damage. Moreover, gestational exposure to the highest dose of DCHP significantly increased ovarian apoptosis and reduced oocyte maturation in female offspring. Collectively, these findings suggest that gestational high-dose DCHP exposure is linked to reduced reproductive potential and ovarian dysfunction in female offspring through oxidative stress-mediated mitophagy, providing new insights into female reproductive dysfunction associated with environmental phthalates.