RESEARCH ARTICLE Microarray expression profiling and co-expression network analysis of circulating LncRNAs and mRNAs associated with neurotoxicity induced by BPA Wei Pang 1 & Fu-Zhi Lian 2 & Xue Leng 3 & Shu-min Wang 1 & Yi-bo Li 1 & Zi-yu Wang 1 & Kai-ren Li 3 & Zhi-xian Gao 1 & Yu-gang Jiang 1 Received: 22 March 2017 /Accepted: 4 March 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract A growing body of evidence has shown bisphenol A (BPA), an estrogen-like industrial chemical, has adverse effects on the nervous system. In this study, we investigated the transcriptional behavior of long non-coding RNAs (lncRNAs) and mRNAs to provide the information to explore neurotoxic effects induced by BPA. By microarray expression profiling, we discovered 151 differentially expressed lncRNAs and 794 differentially expressed mRNAs in the BPA intervention group compared with the control group. Gene ontology analysis indicated the differentially expressed mRNAs were mainly involved in fundamental metabolic processes and physiological and pathological conditions, such as development, synaptic transmission, homeostasis, injury, and neuroinflammation responses. In the expression network of the BPA-induced group, a great number of nodes and connections were found in comparison to the control-derived network. We identified lncRNAs that were aberrantly expressed in the BPA group, among which, growth arrest specific 5 (GAS5) might participate in the BPA-induced neurotoxicity by regulating Jun, RAS, and other pathways indirectly through these differentially expressed genes. This study provides the first investigation of genome-wide lncRNA expression and correlation between lncRNA and mRNA expression in the BPA-induced neurotoxicity. Our results suggest that the elevated expression of lncRNAs is a major biomarker in the neurotoxicity induced by BPA. Keywords Bisphenol A . Neurotoxic biomarkers . Long non-coding RNAs . Co-expression networks Introduction The impacts of endocrine-disrupting compounds on human health and the environment have drawn considerable attention in recent years (Inadera 2015; Mustieles et al. 2015). Bisphenol A (BPA), as the starting material in the production of polycarbonates and epoxy resins, is one of the high produc- tion volume (HPV) chemicals in the world (Suzuki et al. 2000). Humans may have been exposed to BPA in various routes including water, air, soil environment, food contamina- tion, surfaces, and plastic container. BPA exposure has recently been demonstrated to be a risk factor for metabolic disorders and can lead to adverse biological effects on nervous system. To test whether BPA affected neurodevelopment, Yin et al. examined the neural ectoderm specifically during differentia- tion of mouse embryonic stem cells. The expression of four neuroectoderm markers were significantly decreased in BPA intervention samples compared to the controls (Yin et al. 2015). Wang and his colleges found that SH-SY5Y cell line exposure to BPA interfered with protein formation related to AD and led to AD-like neurotoxicity (Wang et al. 2017). These results provided direct evidence of BPA-induced neurotoxicity. Characterization of non-coding RNAs (ncRNAs) has attracted increasing interests in recent years (Wapinski and Wei Pang and Fu-Zhi Lian contributed equally to this work. Responsible editor: Philippe Garrigues * Zhi-xian Gao gaozhx@163.com * Yu-gang Jiang jyg1967@126.com 1 Institute of Environmental and Operational Medicine, Da Li Dao, Tianjin 300050, China 2 Department of Preventive Medicine, Hangzhou Normal University, Hangzhou 310036, China 3 Tianjin Institute of Medical Equipment, Tianjin 300161, China Environmental Science and Pollution Research https://doi.org/10.1007/s11356-018-1678-y