Bisphenol A induces IRE1-dominant endoplasmic reticulum stress, apoptosis, and functional impairment in BeWo trophoblast cells

SAĞ F. B., SEZER Z., GÜZEL MEYDANLI E. E.

Reproductive Toxicology, cilt.141, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 141
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.reprotox.2026.109208
  • Dergi Adı: Reproductive Toxicology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chimica, EMBASE, Environment Index, MEDLINE
  • Anahtar Kelimeler: Apoptosis, Bisphenol A, Endoplasmic reticulum stress, Placenta, Trophoblast cells, Trophoblast differentiation, Unfolded protein response
  • İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet

Özet

Bisphenol A (BPA) is an endocrine-disrupting chemical widely used in polycarbonate plastics and epoxy resins, resulting in human exposure primarily through food-contact materials and thermal paper, as well as environmental sources. Studies suggest that BPA has adverse effects on trophoblast cells, which are critical for placental formation, and that the endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) may contribute to BPA-induced cellular dysfunction. However, the mechanisms by which BPA affects placental trophoblast function remain incompletely understood. This study aimed to explore the connection between ER stress/UPR signaling and BPA-induced trophoblast disfunction. BeWo cells were stimulated with forskolin to induce a syncytium formation, a hallmark of trophoblast differentiation, and then exposed to different concentrations of BPA. The effect of BPA on differentiation and secretion capacity, viability, and apoptosis of the trophoblast cells was examined comparing the results with data related to ER stress. Our findings provide evidence that ER stress/UPR activation is involved in BPA-induced trophoblast dysfunction and that BPA-induced apoptosis may be linked to ER stress. In conclusion, this study offers mechanistic insights into how BPA impacts trophoblast cells and may help in understanding the pregnancy-related adverse outcomes associated with BPA exposure.