Maternal PFBS exposure disrupts oocyte meiotic prophase I and reduces primordial follicle pool

The establishment of the primordial follicle pool during embryogenesis determines the reproductive lifespan of female mammals, and disturbances during meiotic prophase I (MPI) can permanently compromise ovarian reserve. Perfluorobutanesulfonic acid (PFBS), a short-chain replacement for legacy perfluoroalkyl substances (PFAS), is increasingly used in industrial and consumer products, yet its effects on fetal oocyte development remain insufficiently understood. In this study, pregnant ICR mice were orally exposed to PFBS (20 or 200 mg/kg) from 13.5 to 17.5 days post coitum, corresponding to the critical period of meiotic initiation. Maternal PFBS exposure delayed meiotic progression, reflected by the accumulation of pachytene-stage oocytes, without apparent disruption of synapsis. However, PFBS-exposed oocytes showed increased γ-H2A.X, DMC1, and RAD51 foci, indicating impaired DNA double-strand break repair and homologous recombination. Consequently, the number of diplotene-stage oocytes and postnatal primordial follicles was significantly reduced. These findings suggest that prenatal PFBS exposure interferes with homologous recombination–mediated DNA repair during fetal oocyte meiosis, resulting in a diminished ovarian reserve. This work provides mechanistic evidence supporting the potential reproductive toxicity of emerging short-chain PFAS.