Sex Differences in Brain Transcriptomes of Juvenile Cynomolgus Macaques

Background: Behavioral, social, and physical characteristics are posited to distinguish the sexes, yet research on transcription-level sexual differences in the brain is limited. Here, we investigated sexually divergent brain transcriptomics in pre-pubertal cynomolgus macaques, a commonly used surro...

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Main Authors: Nadia Kabbej, Frederick J. Ashby, Alberto Riva, Paul D. Gamlin, Ronald J. Mandel, Aishwarya Kunta, Courtney J. Rouse, Coy D. Heldermon
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/15/5/671
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Summary:Background: Behavioral, social, and physical characteristics are posited to distinguish the sexes, yet research on transcription-level sexual differences in the brain is limited. Here, we investigated sexually divergent brain transcriptomics in pre-pubertal cynomolgus macaques, a commonly used surrogate species to humans. Methods: A transcriptomic profile using RNA sequencing was generated for the temporal lobe, ventral midbrain, and cerebellum of three female and three male cynomolgus macaques previously treated with an adeno-associated virus vector mix. Statistical analyses to determine differentially expressed protein-coding genes in all three lobes were conducted using DeSeq2 with a false-discovery-rate-corrected <i>p</i>-value of 0.05. Results: We identified target genes in the temporal lobe, ventral midbrain, and cerebellum with functions in translation, immunity, behavior, and neurological disorders that exhibited statistically significant sexually divergent expression. Conclusions: We provide potential mechanistic insights into the epidemiological differences observed between the sexes with regard to mental health and infectious diseases, such as COVID-19. Our results provide pre-pubertal information on sexual differences in non-human primate brain transcriptomics and may provide insight into health disparities between the biological sexes in humans.
ISSN:2218-273X