Maternal-fetal transfer of emerging bisphenols: Exposure profile and potential link to latrogenic preterm birth

Bisphenol A (BPA) and its analogues are widely used in consumer products, raising concerns about their health risks, particularly during pregnancy. This study investigated the maternal-fetal transfer of BPA and its 20 alternatives by analyzing first urine samples from 90 newborns in Southern China. Over 95 % of samples contained 2-11 bisphenols, confirming their maternal-fetal transfer and mixed exposure profiles among newborns. The emerging bisphenols bis(3-allyl-4-hydroxyphenyl)sulfone (TGSA) and 4-benzyloxyphenyl 4-hydroxyphenyl sulfone (BPS-MPE) exhibited high detection frequencies of 73-88 % and were strongly correlated (r = 0.326-0.736, p < 0.05), suggesting shared exposure sources. Notably, TGSA exposure was associated with an increased likelihood of iatrogenic preterm birth (OR: 7.90, 95 % CI: 1.22 -51.3). TGSA was the only bisphenol with a transplacental transfer efficiency above 1, indicating effective placental crossing and heightened fetal exposure risks. Molecular docking analyses further revealed strong TGSA binding affinities (-8.3 to -9.2 kcal/mol) with key placental transport proteins-breast cancer resistance protein, serotonin transporter and folate receptor alpha-potentially disrupting placental defense, serotonin signaling and folic acid transport, which may compromise pregnancy outcomes. Given the high detection of TGSA in neonatal urine and its potential impact on fetal development, more attention is needed on bisphenol alternatives and their reproductive toxicity.