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Transcriptomic analysis of key genes involved in sex differences in intellectual development

ZHANG Jia-Wei, ZHENG Xiao-Li, ZHOU Hai-Qian, ZHU Zhen, HAN Wei, YIN Dong-Min^*

Key Laboratory of Brain Functional Genomics, Ministry of Education and Shanghai, School of Life Sciences, East China Normal University, Shanghai 200062, China

Abstract

Intelligence encompasses various abilities, including logical reasoning, comprehension, self-awareness, learning, planning, creativity, and problem-solving. Extensive research and practical experience suggest that there are sex differences in intellectual development, with females typically maturing earlier than males. However, the key genes and molecular network mechanisms underlying these sex differences in intellectual development remain unclear. To date, Genome-Wide Association Studies (GWAS) have identified 507 genes that are significantly associated with intelligence. This study first analyzed RNA sequencing data from different stages of brain development (from BrainSpan), revealing that during the late embryonic stage, the average expression levels of intelligencerelated genes are higher in males than in females, while the opposite is observed during puberty. This study further constructed interaction networks of intelligence-related genes with sex-differential expression in the brain, including the prenatal male network (HELP-M: intelligence genes with higher expression levels in prenatal males) and the pubertal female network (HELP-F: intelligence genes with higher expression levels in pubertal females). The findings indicate that the key genes in both networks are Ep300 and Ctnnb1. Specifically, Ep300 regulates the transcription of 53 genes in both HELP-M and HELP-F, while Ctnnb1 regulates the transcription of 45 genes. Ctnnb1 plays a more prominent role in HELP-M, while Ep300 is more crucial in HELP-F. Finally, this study conducted sequencing validation on rats at different developmental stages, and the results indicated that in the prefrontal cortex of female rats during adolescence, the expression levels of the intelligence genes in HELP-F, as well as key genes Ep300 and Ctnnb1, were higher than those in male rats. These genes were also involved in neurodevelopment-related biological processes. The findings reveal a sex-differentiated intelligence gene network and its key genes, which exhibit varying expression levels during the neurodevelopmental process.

Key words: intellectual development; key genes; sex difference

Received: 　　Accepted:

Corresponding author: 殷东敏　　E-mail:

DOI: 10.13294/j.aps.2024.0079

Citing This Article：

ZHANG Jia-Wei, ZHENG Xiao-Li, ZHOU Hai-Qian, ZHU Zhen, HAN Wei, YIN Dong-Min. Transcriptomic analysis of key genes involved in sex differences in intellectual development. Acta Physiol Sin 2025; 77 (2): 211-221 (in Chinese with English abstract).