Cellular and Molecular Impact of BPA and BPF in mouse and human embryonic stem cell models of dorsal forebrain differentiation

Sammanfattning

Developmental neurotoxicity caused by endocrine-disrupting chemicals is a growing publichealth concern because the developing brain is highly sensitive to environmental exposures.This study aimed to establish in vitro models of dorsal forebrain differentiation using mouseembryonic stem cells (mESCs) and human embryonic stem cells (hESCs), and to investigatethe effects of Bisphenol A (BPA) and Bisphenol F (BPF) on the expression of GRIN2B duringneuronal differentiation.Morphological assessment and reverse transcription quantitative polymerase chain reaction(RT-qPCR) were used to evaluate neuronal differentiation and maturation. The mESC modeldid not show clear neuronal differentiation under the conditions tested. In contrast, hESCderivedcultures successfully differentiated into neurons, displaying neurite-like projectionsand increased expression of neural progenitor and neuronal markers, including PAX6, SOX1,NESTIN, and TUBB3.Differentiating hESC-derived neuronal cultures were exposed to BPA and BPF atconcentrations of 1 nM, 50 nM, and 250 nM. Gene expression analysis showedincreased GRIN2B expression following exposure to 50 nM BPA, while BPF exposure didnot result in clear changes in GRIN2B expression. Expression of NESTIN and TUBB3remained relatively stable following exposure, suggesting that neuronal identity wasmaintained throughout the differentiation process.Overall, this study successfully established an hESC-based dorsal forebrain neuronaldifferentiation model suitable for developmental neurotoxicity research. The findingssuggest that BPA may influence neurodevelopmental signalling pathways involvingGRIN2B during neuronal maturation, while further studies are needed to investigate theunderlying molecular and epigenetic mechanisms and to evaluate potential species- and sexspecificdifferences in bisphenol responses.