Hainan Women and Children's Medical Center, Haikou, China.
NHC Key Laboratory of Control of Tropical Diseases, Hainan Medical University, Haikou, China.
Eur J Neurosci. 2023 Apr;57(7):1184-1196. doi: 10.1111/ejn.15935. Epub 2023 Feb 24.
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.
尽管早期诊断和干预非常重要，但自闭症谱系障碍 (ASD) 的诊断仍然滞后，因为它主要基于 2 岁后出现的临床症状和异常行为。识别自闭症标志物仍然是实现早期有效 ASD 诊断的首要任务。我们之前曾报道过，激素或糖尿病的产前暴露会引发表观遗传变化和氧化应激，导致后代出现类似自闭症的行为和基因抑制。在这里，我们通过外周血单核细胞 (PBMC) 的基因分析建立了一个 ASD 诊断的潜在生物标志物。来自体内小鼠的研究表明，产前激素暴露或母体糖尿病会抑制大脑中雌激素相关受体 α (ERRα)、超氧化物歧化酶 2 (SOD2)、G 蛋白偶联雌激素受体 (GPER) 和维甲酸相关孤儿受体 α (RORA) 的 mRNA 表达以及氧化应激和线粒体功能障碍，随后会引发小鼠后代出现类似自闭症的行为。此外，在造血干细胞 (HSCs) 和 PBMC 中也发现了类似的基因抑制，并在相关启动子上鉴定出了遗传的表观遗传变化。这项人类病例对照研究发现，与正常发育组（n=135）相比，ASD 组（n=132）的 PBMC 中 ERRα、SOD2、GPER 和 RORA 的 mRNA 水平明显降低。ROC 曲线显示 ASD 受试者的曲线下面积为.869±.021，95%置信区间为.829-.909，灵敏度为 1.000，特异性为.856。总之，基于产前因素暴露介导的基因抑制的 PBMC 联合 mRNA 表达可能是 ASD 诊断的潜在生物标志物。
