Abstract：
The etiology of autism spectrum disorder (ASD) is genetic, environmental, and epigenetic. In addition to sex differences in the prevalence of ASD, which is 3-4 times more common in males, there are also distinct clinical, molecular, electrophysiological, and pathophysiological differences between sexes. In human, males with ASD have more externalizing problems (i.e., attention-deficit hyperactivity disorder), more severe communication and social problems, as well as repetitive movements. Females with ASD generally exhibit fewer severe communication problems, less repetitive and stereotyped behavior, but more internalizing problems, such as depression and anxiety. Females need a higher load of genetic changes related to ASD compared to males. There are also sex differences in brain structure, connectivity, and electrophysiology. Genetic or non-genetic experimental animal models of ASD-like behavior, when studied for sex differences, showed some neurobehavioral and electrophysiological differences between male and female animals depending on the specific model. We previously carried out studies on behavioral and molecular differences between male and female mice treated with valproic acid, either prenatally or early postnatally, that exhibited ASD-like behavior and found distinct differences between the sexes, the female mice performing better on tests measuring social interaction and undergoing changes in the expression of more genes in the brain compared to males. Interestingly, co-administration of S-adenosylmethionine alleviated the ASD-like behavioral symptoms and the gene-expression changes to the same extent in both sexes. The mechanisms underlying the sex differences are not yet fully understood.
摘要：
自闭症谱系障碍（ASD）的病因是遗传，环境,和表观遗传。除了ASD患病率的性别差异外，这在男性中更常见3-4倍，也有不同的临床，分子，电生理学,和性别之间的病理生理差异。在人类中,患有ASD的男性有更多的外化问题(即，注意力缺陷多动障碍)，更严重的沟通和社会问题，以及重复的动作。患有ASD的女性通常表现出较少的严重沟通问题，更少的重复和刻板的行为，但是更多的内在化问题，比如抑郁和焦虑。与男性相比，女性需要更高的与ASD相关的遗传变化负荷。大脑结构也有性别差异，连通性,和电生理学。ASD样行为的遗传或非遗传实验动物模型，当研究性别差异时，根据特定的模型，雄性和雌性动物之间显示出一些神经行为和电生理差异。我们以前曾对丙戊酸治疗的雄性和雌性小鼠的行为和分子差异进行研究，无论是产前还是产后早期，表现出类似ASD的行为，并发现两性之间的明显差异，与雄性相比，雌性小鼠在测量社交互动和大脑中更多基因表达变化的测试中表现更好。有趣的是,S-腺苷甲硫氨酸的共同给药减轻了ASD样行为症状，并且两种性别的基因表达变化程度相同。性别差异的潜在机制尚未完全了解。
