Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSPTOLEDO, Victor Hugo Calegari deFELTRIN, Arthur Sant'AnnaBARBOSA, Andre RochaTAHIRA, Ana CarolinaBRENTANI, Helena2022-10-262022-10-262022FRONTIERS IN HUMAN NEUROSCIENCE, v.16, article ID 955607, 21p, 20221662-5161https://observatorio.fm.usp.br/handle/OPI/49354Neurodevetopmental disorders differ considerably between males and females, and fetal brain development is one of the most critical periods to determine risk for these disorders. Transcriptomic studies comparing male and female fetal brain have demonstrated that the highest difference in gene expression occurs in sex chromosomes, but several autossomal genes also demonstrate a slight difference that has not been yet explored. In order to investigate biological pathways underlying fetal brain sex differences, we applied medicine network principles using integrative methods such as co-expression networks (CEMiTool) and regulatory networks (netZoo). The pattern of gene expression from genes in the same pathway tend to reflect biologically relevant phenomena. In this study, network analysis of fetal brain expression reveals regulatory differences between males and females. Integrating two different bioinformatics tools, our results suggest that biological processes such as cell cycle, cell differentiation, energy metabolism and extracellular matrix organization are consistently sex-biased. MSET analysis demonstrates that these differences are relevant to neurodevelopmental disorders, including autism.engopenAccessneurodevelopmental disorderssex differencesfetal brain developmentgene regulatory networkssystems biologyautism spectrum disorder (ASD)transcription factorexpressioncancerdifferentiationcellsneurogenesisphosphorylationmitochondriaarchitecturemetabolismarticleCopyright FRONTIERS MEDIA SA10.3389/fnhum.2022.955607NeurosciencesPsychology