Sex Differences in Brain Transcriptomes of Juvenile Cynomolgus Macaques

Biomolecules. 2025 May 6;15(5):671. doi: 10.3390/biom15050671.

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.

Keywords: COVID-19; behavior; cynomolgus macaques; immunity; pre-pubertal; sexual dimorphism; transcriptomics; translation.

MeSH terms

  • Animals
  • Brain* / metabolism
  • COVID-19 / genetics
  • Cerebellum / metabolism
  • Female
  • Gene Expression Profiling
  • Macaca fascicularis* / genetics
  • Male
  • Sex Characteristics*
  • Temporal Lobe / metabolism
  • Transcriptome*