BPS causes abnormal blastocyst development by inhibiting cell proliferation

In recent years, the escalating global utilization of bisphenol S (BPS) has raised growing concerns regarding its potential adverse effects on human health. However, the effects of BPS exposure on mammalian embryonic development and the associated molecular mechanisms remain inadequately characterized. In this study, we systematically investigated BPS toxicity in mouse embryogenesis by exposing embryos to graded concentrations (0-25 μg/mL). Our results demonstrated a dose-dependent impairment in early embryonic quality following BPS exposure. Specifically, treatment with 10 μg/mL and 15 μg/mL BPS significantly reduced blastocyst formation rates, diminished implantation potential, decreased total cell number of blastocysts, and caused cell fate determination imbalance. Mechanistic studies revealed that under BPS exposure, the massive accumulation of reactive oxygen species (ROS) in embryos induced cell cycle arrest and enhanced autophagy. It is worth noting that the reduction in the total cell number within blastocysts under BPS exposure manifested independently of the apoptotic pathway, as evidenced by the absence of upregulation in caspase 3/7 activity levels and TUNEL-positive signals. Our data collectively reveal that BPS disrupts early embryogenesis through ROS-driven cell cycle dysregulation and erroneous cell fate determination, culminating in compromised blastocyst developmental competence. This research unveils previously unrecognized mechanisms underlying BPS embryotoxicity, emphasizing essential parameters for evaluating chemical reproductive hazards in safety assessments.