Exposure to high doses of tyre antioxidant 6PPD causes senescence to induce unexplained miscarriage by suppressing BAZ1B-mediated ubiquitination degradation of P21 - PubMed
4 hours ago
- #senescence
- #6PPD
- #miscarriage
- High urinary 6PPD levels correlate with villous tissue senescence and miscarriage in humans.
- Mouse studies confirm high-dose 6PPD exposure (≥12 mg/kg/d) leads to placental senescence, causing miscarriage at ≥36 mg/kg/d.
- 6PPD downregulates BAZ1B, inhibiting ubiquitination degradation of P21, increasing P21 protein and inducing cell senescence.
- P21 upregulation results in trophoblast cell senescence, which contributes to miscarriage.
- Therapeutic downregulation of p21, supplementation with Baz1b, or direct senescence suppression reduces placental senescence and miscarriage in mice.