Summary
This study, titled “Sex-specific effects of prenatal bisphenol A exposure on transcriptome-interactome profiles of autism candidate genes in neural stem cells from offspring hippocampus”, investigates how prenatal exposure to Bisphenol A (BPA)—an endocrine-disrupting chemical—affects neural stem cells (NSCs) in the hippocampus of rat offspring. BPA has gained increasing attention as a potential environmental risk factor for autism spectrum disorder (ASD). The research used RNA sequencing, interactome analysis, neurosphere assays, and in vitro cell proliferation studies to identify sex-dependent transcriptomic and functional changes in NSCs exposed to BPA in utero. The altered genes significantly overlapped with known ASD candidate genes and disrupted key neurodevelopmental pathways. The findings suggest that BPA exposure during pregnancy can disrupt NSC development in a sex-specific manner, reinforcing its potential role in ASD pathogenesis.Key Findings
- 648 differentially expressed genes (DEGs) were identified in BPA-exposed hippocampal NSCs, with many overlapping known ASD-related genes (169 from AutismKB and 79 from SFARI).
- Five key ASD-related genes—Atp1a3, Nefl, L1cam, Grin1, Gabrb1—were significantly dysregulated, especially in males.
- DEGs were associated with pathways including GABA/glutamate receptor signaling, synaptic plasticity, and neurological disease functions tied to ASD.
- Neurosphere assays showed that BPA exposure increased neurosphere size but reduced proliferative NSC density, particularly in females.
- Transcriptomic changes in BPA-exposed NSCs correlated strongly with gene expression patterns in iPSC-derived cells from human ASD patients.
- Sex-specific responses were clear, with males exhibiting more robust transcriptomic changes, and females showing enhanced neurosphere growth but reduced proliferation efficiency.
Recommendations
- Recognize BPA as a sex-specific environmental risk factor for ASD.
- Conduct future studies using environmentally relevant BPA doses to better simulate human exposure scenarios.
- Explore BPA effects using human stem cell or brain organoid models to increase translational relevance.
- Investigate underlying epigenetic mechanisms that mediate BPA-induced neurodevelopmental disruptions.
- Advocate for stronger public health regulations limiting prenatal exposure to BPA.
How BPA Exposure Can Occur
1. Dietary Exposure (Primary Route)
- Canned foods and drinks: BPA can leach from the epoxy lining of cans into acidic or fatty contents.
- Plastic containers: Found in water bottles, food containers, baby bottles; leaching increases with heat.
2. Skin Contact
- Thermal paper receipts: BPA transfers from receipts to skin, especially with repeated handling or use of hand sanitizers.
3. Inhalation
- Household dust: BPA found in indoor dust due to consumer electronics, furniture, flooring coatings.
4. Prenatal Exposure
- Placental transfer: BPA crosses the placenta and is detected in fetal blood, placenta, and umbilical cords.
5. Breastfeeding
- Breast milk: BPA can be passed to infants via breast milk after maternal exposure.
6. Medical Devices (Occasionally)
- Plastic tubing or dental sealants: Rare route, more relevant in medical contexts.
Exposure Risk Factors
- Heating food in plastic containers
- Using worn or scratched plastic items
- Frequent handling of receipts
- High consumption of canned or processed food