Effects of Bisphenol A on endogenous retroviral envelopes expression and trophoblast fusion in BeWo cells

• Published in: Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2019-10, Vol.89, p.35-44
• Main Authors: Narciso, Laura, Ietta, Francesca, Romagnoli, Roberta, Paulesu, Luana, Mantovani, Alberto, Tait, Sabrina
• Format: Article
• Language: English
• Subjects: Benzhydryl Compounds - toxicity; Bisphenol A; Cell Fusion; Cell Line; Cell Survival - drug effects; Chorionic Gonadotropin, beta Subunit, Human - metabolism; Endocrine disrupters; Endocrine Disruptors - toxicity; Female; Gene Expression - drug effects; Gene Products, env - genetics; Human endogenous retroviruses; Human placenta; Humans; Phenols - toxicity; Pregnancy; Pregnancy Proteins - genetics; Syncytiotrophoblast; Trophoblasts - drug effects; Trophoblasts - metabolism; Trophoblasts - pathology
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/j.reprotox.2019.07.001

•Bisphenol A promoted the syncytiotrophoblast phenotype in BeWo cells at environmentally relevant concentrations.•Bisphenol A induced trophoblast fusion and secretion of β-hCG in BeWo cells.•Bisphenol A increased the gene expression of three placental endogenous retroviral envelopes ERVWE-1, ERVFRD-1 and ERV3-1.•Bisphenol A increased the protein expression of syncytin-1 and syncytin-2. Placenta is a target organ of Bisphenol A (BPA). To investigate possible effects on syncytiotrophoblast, the exchanging surface between mother and fetus, we exposed a trophoblast model (BeWo) to BPA concentrations occurring in humans (1 and 50 nM). We assessed the gene and protein expression of three human endogenous retroviral envelopes, specifically expressed in placenta (ERVW-1, ERVFRD-1 and ERV3-1), the secretion of β-hCG, the extent of trophoblast fusion and the activity of apoptosis markers (caspases 8, 3, 9 and PARP); additionally, the gene expression of transcription factors regulating HERV expression (i.e. GCM1, PPARγ, ERα and ERβ) was evaluated. At 50 nM, BPA induced ERVW-1, ERVFRD-1 and the corresponding syncytin proteins, ERV3-1, PPARγ, ERα and ERβ expression, increased β-hCG secretion and BeWo cells fusion, thus promoting the syncytiotrophoblast phenotype. The results support placenta as a target organ of BPA. Possible implications on fetal and pregnancy health should be carefully considered.