{"doi":"10.21203/rs.3.rs-723028/v2","title":"Sex Differences in Blood Pressure and the Kidney Cortex Transcriptome in Nonhuman Primates","abstract":"Abstract Hypertension is a complex disease influenced by sex, and genetic and environmental factors. Blood pressure (BP) is a continuous trait that is heritable in primates, including humans and baboons. The kidneys play a role in systemically regulating BP. Sex differences in BP onset and control with antihypertensive drug therapies have been observed in humans and rodents. Hypertension studies in nonhuman primates (NHP) to date have focused on males. We hypothesized that there are differences in renal molecular networks associated with BP in female and male primates. Sodium-naïve female (n=8) and male (n=9) baboons were fed a low-sodium chow diet prior to and during the study. Implantable telemetry devices continuously monitored heart rate and blood pressure over 24-hours, and ultrasound-guided kidney biopsies were collected for RNA-Seq. Serum 17 beta-estradiol concentration correlated BP in females. BP in males correlated with Na + intake, blood urea nitrogen, and glucose. Cell type composition of renal biopsies was consistent between females and males. Sex differences were observed in the kidney transcriptomes by principal components analysis and weighted gene co-expression network analysis. Network analysis revealed HNF4A, ESR1, ESR2, SMARCA4, TP53, and NR3C1 as BP regulators in males. Our results demonstrate sex differences in primate kidney molecular networks and provide evidence of a novel link between renal transcription factors and BP regulation in males. Understanding sex differences and transcriptome variation in primate kidneys correlated with BP and clinical measures associated with BP will inform better therapies towards the goal of precision medicine for women and men.","journal":"Research Square","year":2021,"id":222595,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9181,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":822542,"name":"Kimberly D. Spradling‐Reeves","orcid":"0000-0002-8456-692X","position":1,"is_corresponding":false},{"id":536850,"name":"Robert E. Shade","orcid":"0000-0002-2979-5279","position":2,"is_corresponding":false},{"id":90107,"name":"Sobha Puppala","orcid":null,"position":3,"is_corresponding":false},{"id":823106,"name":"Clinton L. Christensen","orcid":null,"position":4,"is_corresponding":false},{"id":822543,"name":"Shifra Birnbaum","orcid":"0000-0001-7225-9044","position":5,"is_corresponding":false},{"id":423627,"name":"Jeremy P. Glenn","orcid":"0000-0002-1613-034X","position":6,"is_corresponding":false},{"id":245280,"name":"Shannan Hall-Ursone","orcid":"0000-0003-3268-4438","position":7,"is_corresponding":false},{"id":275911,"name":"Laura A. Cox","orcid":"0000-0002-8836-3783","position":8,"is_corresponding":false},{"id":802582,"name":"Angelica M. Riojas","orcid":"0000-0002-4918-407X","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:54:03.549854Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}