Prenatal bisphenol A exposure reprograms SF1-lactylation pathways to promote endometriosis susceptibility.

Endometriosis is an estrogen-dependent disorder influenced by dysregulated steroidogenesis, oxidative stress, and inflammation. Bisphenol A (BPA), a common endocrine disruptor, has been associated with reproductive dysfunction, but its developmental impacts are unclear. We investigated whether prenatal BPA exposure induces lasting endocrine and epigenetic reprogramming that increases endometriosis susceptibility. In human endometrial stromal cells, BPA elevated histone lactylation, SF1, and CYP19A1 expression, oxidative stress, mitochondrial impairment, and inflammatory signaling. In a prenatal BPA mouse model, adult female offspring exhibited increased endometriosis-like lesions and reduced fertility. Pharmacologic inhibition of glycolytic lactate production or SF1 signaling (NaOx, AC45594) partially reversed these outcomes. These findings show that prenatal BPA drives persistent SF1-linked estrogenic activation and lactylation, promoting endometriosis risk and suggesting targeted therapeutic strategies.