Qiao Dan, Mu Chenyu, Chen Huan, Wen Di, Wang Zhao, Zhang Bohan, Guo Fangzhen, Wang Chang, Zhang Rong, Wang Chongying, Cui Huixian, Li Sha
Department of Human Anatomy; Neuroscience Research Center, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Neurodegenerative Disease Mechanism, Shijiazhuang 050017, China.
College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Shijiazhuang 050017, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Jan 10;136:111219. doi: 10.1016/j.pnpbp.2024.111219. Epub 2024 Dec 16.
Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder that significantly jeopardizes the physical and mental well-being of children. Autism spectrum disorder results from a combination of environmental and genetic factors. Hyperandrogenic exposure during pregnancy increases their risk of developing autism. Nevertheless, the prenatal exposure to androgens affects offspring neurodevelopment and the underlying mechanisms have not been fully elucidated. In the present study, administration of excessive dihydrotestosterone (DHT) to pregnant mice was found to impair neuronal development and dendritic spine formation in offspring, inducing autism-like behaviors. Furthermore, through mRNA transcriptome sequencing technology, the key molecule Nr4a2 was identified during this process of change. Overexpression of Nr4a2 and treatment with amodiaquine (AQ) significantly improved the abnormal phenotypes in offspring caused by prenatal exposure to androgens. Overall, Nr4a2 emerges as a crucial molecule involved in the impairment of offspring neurodevelopment due to prenatal androgen exposure, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms.
自闭症谱系障碍（ASD）是一种高度异质性的神经发育障碍，严重危及儿童的身心健康。自闭症谱系障碍是由环境和遗传因素共同作用导致的。孕期雄激素暴露增加了儿童患自闭症的风险。然而，产前雄激素暴露对后代神经发育的影响及其潜在机制尚未完全阐明。在本研究中，发现给怀孕小鼠注射过量双氢睾酮（DHT）会损害后代的神经元发育和树突棘形成，诱发自闭症样行为。此外，通过mRNA转录组测序技术，在此变化过程中鉴定出关键分子Nr4a2。Nr4a2的过表达和氨氯喹（AQ）处理显著改善了产前雄激素暴露所致后代的异常表型。总体而言，Nr4a2是产前雄激素暴露导致后代神经发育受损的关键分子，为深入研究影响因素和潜在机制提供了新视角。
