ArticleGenome research2022
Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation.
Article in Genome research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 57 citations in OpenAlex.
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- Long-Term Follow-Up of Patients With Mitochondrial Carbonic Anhydrase VA Deficiency. A Case Report and Literature Review.JIMD reports · 2026Article
- Androgen excess uncouples circulating and hepatic lipid homeostasis in females on a high-calorie diet.Journal of lipid research · 2026Article
- Sex differences in congenital hereditary endothelial dystrophy (CHED) and Slc4a11Biology of sex differences · 2026Article
- Effects of testosterone on gene expression in males and females across 40 human tissues.Scientific reports · 2026Article
- KDM5C and KDM5D influence DNA methylation in adult mouse liver.Biology of sex differences · 2026Article
- Integrated chromatin and transcriptomic profiling reveals sex-specific mechanisms of gene regulation in hepatic nutrient responses.PLoS biology · 2026Article
- Gene dosage imbalance disrupts systemic metabolism in the Dp16 Down syndrome mouse model.bioRxiv : the preprint server for biology · 2026Article
- Host biological sex directs immune control of theFrontiers in immunology · 2026Article
- Impact of sperm fractionation on chromosome positioning, chromatin integrity, DNA methylation, and hydroxymethylation level.Cellular & molecular biology letters · 2025Article
- Sex-dependent relationships between PFAS and placental transcriptomics identified by weighted gene co-expression analysis.Environmental research · 2025Article
- A human induced pluripotent stem cell toolbox for studying sex chromosome effects.Stem cell reports · 2025Article
- Incorporating transcriptomic data into genomic prediction models to improve the prediction accuracy of phenotypes of efficiency traits.Genetics, selection, evolution : GSE · 2025Article
- Influence of Gonadal and Chromosomal Sex on the Brain Transcriptome in a Mouse Species with Natural Sex Reversal.Molecular biology and evolution · 2025Article
- Sex Differences in the Lacrimal Gland: Implications for Dry Eye Disease.International journal of molecular sciences · 2025Review
- Roles of chromosomal and gonadal sex in the fetal and placental responses to maternal food restriction in mice.Molecular human reproduction · 2025Article
- Survey of gene, lncRNA and transposon transcription patterns in four mouse organs highlights shared and organ-specific sex-biased regulation.Genome biology · 2025Article
- The role of motivation in eating disorders: understanding sex differences in the circuits.Frontiers in behavioral neuroscience · 2025Review
- Combined effects of genetic background and diet on mouse metabolism and gene expression.iScience · 2024Article
- Regulation of Sex-biased Gene Expression by the Ancestral X-Y Chromosomal Gene PairbioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Sex differences in physiology and disease in mammals result from the effects of three classes of factors that are inherently unequal in males and females: reversible (activational) effects of gonadal hormones, permanent (organizational) effects of gonadal hormones, and cell-autonomous effects of sex chromosomes, as well as genes driven by these classes of factors. Often, these factors act together to cause sex differences in specific phenotypes, but the relative contribution of each and the interactions among them remain unclear. Here, we used the four core genotypes (FCG) mouse model with or without hormone replacement to distinguish the effects of each class of sex-biasing factors on transcriptome regulation in liver and adipose tissues. We found that the activational hormone levels have the strongest influence on gene expression, followed by the organizational gonadal sex effect, and last, sex chromosomal effect, along with interactions among the three factors. Tissue specificity was prominent, with a major impact of estradiol on adipose tissue gene regulation and of testosterone on the liver transcriptome. The networks affected by the three sex-biasing factors include development, immunity and metabolism, and tissue-specific regulators were identified for these networks. Furthermore, the genes affected by individual sex-biasing factors and interactions among factors are associated with human disease traits such as coronary artery disease, diabetes, and inflammatory bowel disease. Our study offers a tissue-specific account of the individual and interactive contributions of major sex-biasing factors to gene regulation that have broad impact on systemic metabolic, endocrine, and immune functions.
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