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Bisphenol A-sulfate conjugate disrupts AURKA transcription and cell cycle in BeWo cytotrophoblasts

Jumpei Fujiki1, Megumi Uchida1, Sakurako Tsunoda1

  • 1Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, 069-8501, Japan.

Molecular and Cellular Endocrinology
|January 18, 2022
PubMed

Insights

Bisphenol A sulfate (BPA-S) inhibits human placental cell growth by reactivating the sulfate-sulfatase pathway, leading to cell cycle arrest. This suggests potential risks from reactivated endocrine-disrupting chemicals.

Area of Science:

  • Endocrinology
  • Toxicology
  • Cell Biology

Background:

  • Bisphenol A (BPA) is known for reproductive toxicity.
  • BPA is typically inactivated by conjugation, but the toxicity of metabolites is unclear.
  • The placenta utilizes the sulfate-sulfatase pathway for steroid transport and reactivation.

Purpose of the Study:

  • To investigate the adverse effects of Bisphenol A sulfate (BPA-S) on human placental BeWo cytotrophoblasts.
  • To determine if BPA-S utilizes the sulfate-sulfatase pathway for its effects.

Main Methods:

  • Exposure of BeWo cells to BPA-S and unconjugated BPA.
  • Treatment with inhibitors of organic anion-transporting peptides (OATPs) and sulfatase (STS).
  • Gene expression analysis for OATP1A2, OATP4A1, and STS.
  • Cell cycle analysis and Aurora kinase A (AURKA) transcript quantification.

Main Results:

  • High-concentration BPA-S inhibited BeWo cell growth, similar to BPA.
  • Growth inhibition was reversed by OATP and STS inhibitors.
  • BPA-S increased G2/M phase cell cycle arrest and decreased AURKA transcript levels.
  • BeWo cells express OATP1A2, OATP4A1, and STS, supporting pathway involvement.

Conclusions:

  • BPA-S suppresses BeWo cytotrophoblast proliferation and induces cell cycle arrest via the sulfate-sulfatase pathway.
  • Decreased AURKA expression is implicated in BPA-S-induced cell cycle arrest.
  • Findings highlight the potential risks of reactivated sulfated endocrine-disrupting chemicals.
Keywords:
BPABisphenolEndocrine-disrupting chemicals (EDCs)PlacentaSulfate-sulfatase pathway

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