ArticleBiology of sex differences2025
Sex-related differences and associated transcriptional signatures in the brain ventricular system and cerebrospinal fluid development in full-term neonates.
Article in Biology of sex differences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe cerebrospinal fluid (CSF) is known to serve as a unique environment for neurodevelopment, with specific proteins secreted by epithelial cells of the choroid plexus (CP) playing crucial roles in cortical development and cell differentiation. Sex-related differences in the brain in early life have been widely identified, but few studies have investigated the neonatal CSF system and associated transcriptional signatures.
methodsThis study included 75 full-term neonates [44 males and 31 females; gestational age (GA) = 37-42 weeks] without significant MRI abnormalities from the dHCP (developing Human Connectome Project) database. Deep-learning automated segmentation was used to measure various metrics of the brain ventricular system and CSF. Sex-related differences and relationships with postnatal age were analyzed by linear regression. Correlations between the CP and CSF space metrics were also examined. LASSO regression was further applied to identify the key genes contributing to the sex-related CSF system differences by using regional gene expression data from the Allen Human Brain Atlas.
resultsRight lateral ventricles [2.42 ± 0.98 vs. 2.04 ± 0.45 cm3 (mean ± standard deviation), p = 0.036] and right CP (0.16 ± 0.07 vs. 0.13 ± 0.04 cm3, p = 0.024) were larger in males, with a stronger volume correlation (male/female correlation coefficients r: 0.798 vs. 0.649, p < 1 × 10
conclusionMale neonates present larger volumes and faster growth of the right lateral ventricle, likely linked to corresponding CP volume and growth pattern. The downregulation of DERL2 and upregulation of MRPL48 may contribute to these sex-related variations in the CSF system, suggesting a molecular basis for sex-specific brain development.
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