# Sex Differences in Brain Transcriptomes of Juvenile Cynomolgus Macaques

## TL;DR

This study finds sex-based differences in brain gene activity in young macaques, which could help explain health disparities between males and females.

## Contribution

The study reveals pre-pubertal sexually divergent gene expression in non-human primate brains, offering new insights into sex-based health differences.

## Key findings

- Sexually divergent genes in brain regions are linked to translation, immunity, behavior, and neurological disorders.
- Significant differences in gene expression were found in the temporal lobe, ventral midbrain, and cerebellum.
- Findings may explain epidemiological differences in mental health and infectious diseases between sexes.

## Abstract

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 p-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.