{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:00:31Z","timestamp":1773392431366,"version":"3.50.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Basic and Clinical Collaborative Research Program of Anhui Medical University","award":["2022xkjT020"],"award-info":[{"award-number":["2022xkjT020"]}]},{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82201777"],"award-info":[{"award-number":["82201777"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hypoactive sexual desire disorder (HSDD), a prevalent condition affecting sexual health in women, is induced by imbalanced neurobiological regulation of excitatory and inhibitory pathways associated with sexual response. The prefrontal cortex (PFC) is a key region in the sexual desire response pathway. Nevertheless, the cellular dynamics and molecular mechanisms driving the pathophysiology of HSDD remain unclear, limiting targeted therapeutic development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To explore the cellular and molecular mechanisms of HSDD using a female rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established a translational HSDD model using female Sprague\u2013Dawley rats with low sexual desire. Subsequently, single-nucleus RNA sequencing (snRNA-seq) and multimodal bioinformatics analyses were used to comprehensively characterize cellular diversity and transcriptional signatures in the PFC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>Primary: neuronal\/glial composition; secondary: disease-relevant pathway dysregulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SnRNA-seq profiling revealed altered PFC cell composition in rats with low sexual desire (LSD), with increased proportions of inhibitory neuron subtypes (Inh1-3) and microglia, concomitant reductions in excitatory neuron populations (Ex1 and Ex3), and disrupted oligodendrocyte precursor cell (OPC) maturation. Transcriptomic analysis revealed 506 differentially expressed genes (DEGs), of which 91.3% were downregulated in the LSD group. Enrichment analyses linked the DEGs to mitochondrial dysfunction, lysosomal function, and neurodegenerative disease-associated pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical implications<\/jats:title>\n                    <jats:p>These preliminary findings potentially advance our understanding of HSDD neurobiology, and identify testable targets for therapeutic intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Strengths &amp; limitations<\/jats:title>\n                    <jats:p>The high-throughput analysis offered detailed information, but the small sample size and potential confounding factors in phenotype classification were limitations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We have established a stable translational model of HSDD through rigorous screening and validation, demonstrating specific molecular and cellular alterations in the PFC of model rats characterized by: (1) excitatory-inhibitory neuronal imbalance, (2) microglial activation indicative of neuroimmune dysregulation, and (3) OPC maturation deficits.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jsxmed\/qdaf138","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T07:40:12Z","timestamp":1748504412000},"page":"1911-1922","source":"Crossref","is-referenced-by-count":2,"title":["Single-nucleus RNA sequencing reveals cellular and molecular signatures in the prefrontal cortex of a hypoactive sexual desire disorder rat model"],"prefix":"10.1093","volume":"22","author":[{"given":"Mengyue","family":"Chen","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui, 230032 ,","place":["China"]},{"name":"National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract , Hefei, Anhui, 230032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingfang","family":"Guan","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui, 230032 ,","place":["China"]},{"name":"National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract , Hefei, Anhui, 230032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui, 230032 ,","place":["China"]},{"name":"National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract , Hefei, Anhui, 230032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Song","sequence":"additional","affiliation":[{"name":"Key Laboratory of Population Health Across Life Cycle, Ministry of Education of the People\u2019s Republic of China , Hefei, Anhui, 230032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Population Health Across Life Cycle, Ministry of Education of the People\u2019s Republic of China , Hefei, Anhui, 230032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojin","family":"He","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui, 230032 ,","place":["China"]},{"name":"Reproductive Medicine Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , 200030,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui, 230032 ,","place":["China"]},{"name":"National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract , Hefei, Anhui, 230032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanjian","family":"Li","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui, 230032 ,","place":["China"]},{"name":"National Health Commission Key Laboratory of Study on Abnormal Gametes and Reproductive Tract , Hefei, Anhui, 230032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"issue":"6","key":"2025110819150360200_ref1","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1111\/j.1743-6109.2009.01309.x","article-title":"Pathways of sexual desire","volume":"6","author":"Pfaus","year":"2009","journal-title":"J Sex Med"},{"issue":"07","key":"2025110819150360200_ref2","doi-asserted-by":"publisher","first-page":"821","DOI":"10.4088\/JCP.10bs06117blu","article-title":"Targeting circuits of sexual desire as a treatment strategy for hypoactive sexual desire disorder","volume":"71","author":"Stahl","year":"2010","journal-title":"J Clin Psychiatry"},{"issue":"1","key":"2025110819150360200_ref3","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.mayocp.2016.09.018","article-title":"Hypoactive sexual desire disorder: International Society for the Study of Women's sexual health (ISSWSH) expert consensus panel review","volume":"92","author":"Goldstein","year":"2017","journal-title":"Mayo Clin Proc"},{"issue":"5","key":"2025110819150360200_ref4","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1089\/jwh.2011.3002","article-title":"Sexual desire problems in women seeking healthcare: a novel study design for ascertaining prevalence of hypoactive sexual desire disorder in clinic-based samples of U.S. women","volume":"21","author":"Rosen","year":"2012","journal-title":"J Women's Health (Larchmt)"},{"issue":"2","key":"2025110819150360200_ref5","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1002\/ijgo.14205","article-title":"Low sexual desire and hypoactive sexual desire disorder in Chinese women","volume":"158","author":"Li","year":"2022","journal-title":"Int J Gynaecol Obstet"},{"issue":"11","key":"2025110819150360200_ref6","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1007\/s40263-015-0288-1","article-title":"The female sexual response: current models, neurobiological underpinnings and agents currently approved or under investigation for the treatment of hypoactive sexual desire disorder","volume":"29","author":"Kingsberg","year":"2015","journal-title":"CNS Drugs"},{"issue":"2","key":"2025110819150360200_ref7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.esxm.2018.01.004","article-title":"Evaluation and Management of Hypoactive Sexual Desire Disorder","volume":"6","author":"Clayton","year":"2018","journal-title":"Sex Med"},{"issue":"6","key":"2025110819150360200_ref8","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3810\/pgm.2010.11.2230","article-title":"Low sexual desire--is it all in her head? Pathophysiology, diagnosis, and treatment of hypoactive sexual desire disorder","volume":"122","author":"Simon","year":"2010","journal-title":"Postgrad Med"},{"issue":"2","key":"2025110819150360200_ref9","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1002\/smrj.14","article-title":"Animal models for the study of female sexual dysfunction","volume":"1","author":"Marson","year":"2013","journal-title":"Sex Med Rev"},{"issue":"4","key":"2025110819150360200_ref10","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/0018-506X(89)90037-8","article-title":"Solicitation behavior in the estrous female rat: a review","volume":"23","author":"Erskine","year":"1989","journal-title":"Horm Behav"},{"issue":"3","key":"2025110819150360200_ref11","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.pbb.2004.04.013","article-title":"Preclinical models of sexual desire: conceptual and behavioral analyses","volume":"78","author":"Agmo","year":"2004","journal-title":"Pharmacol Biochem Behav"},{"issue":"3","key":"2025110819150360200_ref12","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.yhbeh.2004.11.012","article-title":"Sexual behavior of female rats in a multiple-partner preference test","volume":"47","author":"Ferreira-Nuno","year":"2005","journal-title":"Horm Behav"},{"issue":"1","key":"2025110819150360200_ref13","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0166-4328(99)00087-X","article-title":"What do female rats like about sex?","volume":"105","author":"Paredes","year":"1999","journal-title":"Paced Mating Behav Brain Res"},{"issue":"1","key":"2025110819150360200_ref14","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/j.1743-6109.2010.01998.x","article-title":"A new female rat animal model for hypoactive sexual desire disorder; behavioral and pharmacological evidence","volume":"8","author":"Snoeren","year":"2011","journal-title":"J Sex Med"},{"issue":"9","key":"2025110819150360200_ref15","doi-asserted-by":"publisher","first-page":"2970","DOI":"10.1111\/j.1743-6109.2010.01960.x","article-title":"Experimental models for the study of female and male sexual function","volume":"7","author":"Giuliano","year":"2010","journal-title":"J Sex Med"},{"issue":"6","key":"2025110819150360200_ref16","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1111\/jmwh.13283","article-title":"Hypoactive sexual desire disorder in women: physiology, assessment, diagnosis, and treatment","volume":"66","author":"Pettigrew","year":"2021","journal-title":"J Midwifery Womens Health"},{"issue":"1","key":"2025110819150360200_ref17","doi-asserted-by":"publisher","first-page":"4183","DOI":"10.1038\/s41467-020-17876-0","article-title":"A single-cell atlas of the human substantia nigra reveals cell-specific pathways associated with neurological disorders","volume":"11","author":"Agarwal","year":"2020","journal-title":"Nat Commun"},{"key":"2025110819150360200_ref18","doi-asserted-by":"publisher","first-page":"101422","DOI":"10.1016\/j.molmet.2021.101422","article-title":"Single nuclei RNA sequencing of the rat AP and NTS following GDF15 treatment","volume":"56","author":"Reiner","year":"2022","journal-title":"Mol Metab"},{"issue":"1","key":"2025110819150360200_ref19","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/0304-3959(94)00150-D","article-title":"Behavioral responses to uterine or vaginal distension in the rat","volume":"61","author":"Berkley","year":"1995","journal-title":"Pain"},{"issue":"2","key":"2025110819150360200_ref20","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/S0304-3959(99)00049-4","article-title":"Estrous variations in behavioral responses to vaginal and uterine distention in the rat","volume":"82","author":"Bradshaw","year":"1999","journal-title":"Pain"},{"issue":"4","key":"2025110819150360200_ref21","doi-asserted-by":"publisher","first-page":"888","DOI":"10.17305\/bb.2024.10221","article-title":"Exploratory genetic analysis in children with autism spectrum disorder and other developmental disorders using whole exome sequencing","volume":"24","author":"Hamzic","year":"2024","journal-title":"Biomol Biomed"},{"issue":"D1","key":"2025110819150360200_ref22","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2025110819150360200_ref23","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.bbi.2024.08.016","article-title":"Proteomic evidence of depression-associated astrocytic dysfunction in the human male olfactory bulb","volume":"122","author":"Rahimian","year":"2024","journal-title":"Brain Behav Immun"},{"key":"2025110819150360200_ref24","doi-asserted-by":"publisher","first-page":"101122","DOI":"10.1016\/j.yfrne.2024.101122","article-title":"Cholecystokinin (CCK): a neuromodulator with therapeutic potential in Alzheimer's and Parkinson's disease","volume":"73","author":"Reich","year":"2024","journal-title":"Front Neuroendocrinol"},{"key":"2025110819150360200_ref25","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.19.24306098","article-title":"Comparative gene regulatory networks modulating APOE expression in microglia and astrocytes","author":"Brase","year":"2024","journal-title":"medRxiv."},{"issue":"4","key":"2025110819150360200_ref26","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat Biotechnol"},{"issue":"3","key":"2025110819150360200_ref27","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.pbb.2005.10.007","article-title":"\"coffee, tea and me\": moderate doses of caffeine affect sexual behavior in female rats","volume":"82","author":"Guarraci","year":"2005","journal-title":"Pharmacol Biochem Behav"},{"issue":"1","key":"2025110819150360200_ref28","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.brainres.2003.10.056","article-title":"Paced mating behavior in the female rat following lesions of three regions responsive to vaginocervical stimulation","volume":"999","author":"Guarraci","year":"2004","journal-title":"Brain Res"},{"issue":"5","key":"2025110819150360200_ref29","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1111\/jsm.12094","article-title":"Flibanserin treatment increases appetitive sexual motivation in the female rat","volume":"10","author":"Gelez","year":"2013","journal-title":"J Sex Med"},{"issue":"2","key":"2025110819150360200_ref30","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1056\/NEJMp1513686","article-title":"FDA approval of Flibanserin--treating hypoactive sexual desire disorder","volume":"374","author":"Joffe","year":"2016","journal-title":"N Engl J Med"},{"issue":"14","key":"2025110819150360200_ref31","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1007\/s40265-019-01187-w","article-title":"Bremelanotide: first approval","volume":"79","author":"Dhillon","year":"2019","journal-title":"Drugs"}],"container-title":["The Journal of Sexual Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/22\/11\/1911\/64286064\/qdaf138.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jsm\/article-pdf\/22\/11\/1911\/64286064\/qdaf138.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:15:07Z","timestamp":1762647307000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jsm\/article\/22\/11\/1911\/8255902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,16]]},"references-count":31,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,9,16]]},"published-print":{"date-parts":[[2025,11,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jsxmed\/qdaf138","relation":{},"ISSN":["1743-6095","1743-6109"],"issn-type":[{"value":"1743-6095","type":"print"},{"value":"1743-6109","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,9,16]]}}}