Hypoxia-induced metabolic shifting and AHR/BCRP axis impairment drive placental dysfunction in early-onset preeclampsia and FGR.

Background: Placental hypoxia and vascular dysfunction are hallmarks of preeclampsia (PE). The Breast Cancer Resistance Protein (BCRP) is critical for maintaining the placental barrier against oxidative stress. We investigated whether the hypoxic microenvironment drives BCRP dysregulation and how this correlates with fetal growth restriction (FGR) in severe preeclampsia. Methods: This case-control study enrolled 59 normotensive and 72 preeclamptic pregnancies to compare clinical phenotypes and placental BCRP expression across distinct gestational age subgroups. Mechanistic investigations were conducted using human BeWo trophoblasts under pathological hypoxia (1%O Results: Clinically, patients with early-onset preeclampsia (28-33 Conclusion: Our study defines a distinct "dual-hit" molecular phenotype in early-onset preeclampsia. Chronic hypoxia not only drives an acute metabolic crisis but also actively dismantles the protective AHR/BCRP placental barrier via HIF-1α-mediated ARNT sequestering. This synergistic failure compromises placental xenobiotic detoxification, exacerbates fetal toxicological vulnerability, and fundamentally contributes to the profound severity of FGR.