Prenatal exposure of diabetes and progestin‐mediated autistic biomarker in peripheral blood mononuclear cells

• Published in: The European journal of neuroscience Vol. 57; no. 7; pp. 1184 - 1196
• Main Authors: Jiao, Yun, Wang, Min, Li, Huilin, Jia, Qingzheng, Xu, Lichao, Zhong, Liyan, Huang, Jingwen, Li, Ling, Xiang, Wei, Yao, Paul
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.04.2023
• Subjects: Animals; Autism; Autism Spectrum Disorder - genetics; Autism Spectrum Disorder - metabolism; Autistic Disorder; Biomarkers; Case-Control Studies; Diabetes; Diabetes Mellitus; Diagnosis; Epigenetics; Estrogen receptors; Estrogens; Female; Gene expression; Hematopoietic stem cells; hormone; Humans; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Mice; Mitochondria; Oxidative stress; PBMC; Peripheral blood mononuclear cells; Pregnancy; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects; Progestin; Progestins; Retinoic acid; RNA, Messenger; Superoxide dismutase; PBMC; diabetes; autism; oxidative stress; hormone
• ISSN: 0953-816X; 1460-9568; 1460-9568
• DOI: 10.1111/ejn.15935

Despite the importance of early diagnosis and intervention, the diagnosis of autism spectrum disorders (ASDs) remains delayed as it is mostly based on clinical symptoms and abnormal behaviours appearing after 2 years of age. Identification of autistic markers remains a top priority in achieving an early and effective ASD diagnosis. We have previously reported that prenatal exposure of hormones or diabetes triggers epigenetic changes and oxidative stress, resulting in gene suppression with autism‐like behaviours in offspring. Here, a potential biomarker for ASD diagnosis was established through gene analysis in peripheral blood mononuclear cells (PBMCs). The study from in vivo mouse showed that prenatal hormone exposure or maternal diabetes suppresses mRNA expression of estrogen‐related receptor α (ERRα), superoxide dismutase 2 (SOD2), G protein‐coupled estrogen receptor (GPER) and retinoic acid‐related orphan receptor α (RORA) in the brain as well as oxidative stress and mitochondrial dysfunction, subsequently triggering autism‐like behaviour in mouse offspring. Also, similar gene suppression was found in hematopoietic stem cells (HSCs) and PBMC, with inherited epigenetic changes being identified on the related promoters. The human case–control study found that mRNA levels of ERRα, SOD2, GPER and RORA were significantly reduced in PBMC from ASD subjects (n = 132) compared with typically developing (n = 135) group. The receiver operating characteristic curve showed a .869 ± .021 of area under the curve for ASD subjects with 95% confidence interval of .829–.909, together with 1.000 of sensitivity and .856 of specificity. In conclusion, the combined mRNA expression in PBMC based on prenatal factor exposure‐mediated gene suppression could be a potential biomarker for ASD diagnosis. Prenatal factor exposure induces epigenetic changes and oxidative stress in autistic offspring. Epigenetic changes trigger gene suppression in brain tissues and peripheral blood mononuclear cells (PBMCs). Gene expression of ERRα, GPER, RORA and SOD2 is reduced in PBMC in autistic subjects compared with typically developing subjects. Combined gene suppression in PBMC can be a potential biomarker for autism screening.