Alleviating effects of Semen Cuscutae flavonoids on bisphenol A-induced reproductive toxicity in mice offspring

Document Type : Original Article

Authors

1 School of Life Sciences and Food Engineering, Hebei University of Engineering, Handan, China

2 Bethune International Peace Hospital, Shijiazhuang, China

Abstract
Bisphenol A (BPA), a typical environmental endocrine disruptor, induces trans-generational reproductive injury in animals and humans. This study investigated the protective effects and mechanisms of Semen Cuscutae flavonoids (SCFs) against pre-natal BPA exposure-induced reproductive toxicity in male and female mice offspring. Pregnant Kunming mice were intragastrically administered corn oil (control), 50.00 mg kg-1 per day BPA (BPA group), or combined 50.00 mg kg-1 per day BPA and 1.00 mg kg-1 per day SCFs (BPA+SCF group) from gestation day one to gestation day 14. Serum, testes and ovaries from 8-week-old offspring mice were collected, and multiple reproductive-related indicators were detected via enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase-mediated dUTP nick‑end labeling, immunohistochemistry, and RT-qPCR. Results showed that pre-natal BPA exposure significantly reduced serum testosterone in male offspring, and elevated estradiol while suppressed follicle stimulating hormone and luteinizing hormone in female offspring, accompanied by abnormal gonadal histomorphology and sharply increased gonadal apoptotic cells. At the molecular level, BPA down-regulated steroidogenic genes, including steroidogenic acute regulatory protein and CYP11α, and folliculogenesis-related KIT ligand, up-regulated ovarian anti-Müllerian hormone, disturbed pro-apoptotic Bax/ anti-apoptotic Bcl-2 balance. The SCFs intervention reversed BPA-induced hormonal disorders and gonadal histological lesions. Mechanistically, SCFs up-regulated Bcl-2 and down-regulated Bax genes to reduce gonadal apoptosis. Meanwhile, SCFs restored the mRNA and protein expressions of Steroidogenic acute regulatory protein, CYP11α, KIT ligand and anti-Müllerian hormone. In conclusion, SCFs exert protective effects against pre-natal BPA-triggered offspring reproductive toxicity by balancing apoptotic signaling and modulating steroidogenic and folliculogenic genes expressions.

Keywords

Subjects

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Volume 17, Issue 10
October 2026
Pages 709-719

  • Receive Date 22 September 2025
  • Revise Date 18 July 2026
  • Accept Date 17 August 2026