Esr1-dependent signaling and transcriptional maturation in the medial preoptic area of the hypothalamus shape the development of mating behavior during adolescence
Year: 2026
Type: article
Abstract: Mating and other behaviors emerge during adolescence through the coordinated actions of steroid hormone signaling throughout the nervous system and periphery. In this study, we investigated the transcriptional dynamics of the medial preoptic area (MPOA), a critical region for reproductive behavior, using single-cell RNA sequencing (scRNA-seq) and in situ hybridization techniques in male and female mice throughout adolescence development. Our findings reveal that estrogen receptor 1 (Esr1) plays a pivotal role in the transcriptional maturation of GABAergic neurons within the MPOA during adolescence. Deletion of the estrogen receptor gene, Esr1, in GABAergic neurons (Vgat+) disrupted the developmental progression of mating behaviors in both sexes, while its deletion in glutamatergic neurons (Vglut2+) had no observable effect. In males and females, these neurons displayed distinct transcriptional trajectories, with hormone-dependent gene expression patterns emerging throughout adolescence and regulated by Esr1. Esr1 deletion in MPOA GABAergic neurons, prior to adolescence, arrested adolescent transcriptional progression of these cells and uncovered sex-specific gene-regulatory networks associated with Esr1 signaling. Our results underscore the critical role of Esr1 in orchestrating sex-specific transcriptional dynamics during adolescence, revealing gene regulatory networks implicated in the development of hypothalamic-controlled reproductive behaviors.
Source: UNC Libraries
DOI: 10.17615/pm8z-a431
Authors: Siputro, Jason, Ahmad, Omar, Rossi, Mark, Basiri, Marcus L, Simon, Rhiana, Soetedjo, James, Briones, Brandy, Zweifel, Larry S, Palmiter, Richard D, Liu, Yuejia, Johnston, Nathan, Hashikawa, Koichi, Hashikawa, Yoshiko, Rubinow, David, Stuber, Garret D, Chen, Jane Y, McHenry, Jenna, Ishii, Kentaro K, Mukundan, Rishi
Institution: University of North Carolina at Chapel Hill
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, Howard Hughes Medical Institute, U.S. Department of Agriculture, Bill and Melinda Gates Foundation, Brain and Behavior Research Foundation, American Heart Association, European Molecular Biology Organization, City University of Hong Kong, University of Pittsburgh, Japan Agency for Medical Research and Development, Wellcome Trust, Maryland Stem Cell Research Fund, Shanghai Science and Technology Development Foundation, Comunidad de Madrid, Ministerio de Ciencia, Innovación y Universidades, Bloomberg Philanthropies, Centres de Recerca de Catalunya, British Heart Foundation, Royal Society, Gatsby Charitable Foundation, European Commission, European Centre for Disease Prevention and Control, Deutsche Forschungsgemeinschaft, Volkswagen Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Fundação de Amparo à Pesquisa do Estado de São Paulo, National Natural Science Foundation of China, Chinese Academy of Sciences, Generalitat de Catalunya, China Postdoctoral Science Foundation, Consejo Nacional de Ciencia y Tecnología, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Generalitat Valenciana, Ministero dell’Istruzione, dell’Università e della Ricerca, Natural Science Foundation of Guangdong Province, National Research Foundation of Korea, Natural Science Foundation of Hebei Province, Natural Science Foundation of Hubei Province, Mazandaran University of Medical Sciences, Natural Science Foundation of Jiangsu Province, Mashhad University of Medical Sciences, Centre National de la Recherche Scientifique, Ministerio de Ciencia e Innovación, Natural Science Foundation of Henan Province, Forskningsrådet om Hälsa, Arbetsliv och Välfärd, Natural Science Foundation of Shandong Province, Universidad de Sonora, Deutsches Zentrum für Lungenforschung, University of Phayao, Thailand Science Research and Innovation, Ministero dell'Università e della Ricerca, National Institutes of Health, Albert Einstein College of Medicine, Yeshiva University, Horizon 2020 Framework Programme, Australian Research Council, National Health and Medical Research Council, Japan Society for the Promotion of Science, Japan Science and Technology Agency, Staatssekretariat für Bildung, Forschung und Innovation, European Regional Development Fund, Institute for Information and Communications Technology Promotion, Erasmus+, Zabol University of Medical Sciences, Agencia Estatal de Investigación, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, Agricultural Science and Technology Innovation Program, National Key Research and Development Program of China Stem Cell and Translational Research, Science and Technology Program of Gansu Province, Landbrugsstyrelsen, Basic and Applied Basic Research Foundation of Guangdong Province, National Institute on Aging, Office of Naval Research, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute for Occupational Safety and Health, European Social Fund, Air Force Office of Scientific Research, H2020 European Research Council, H2020 Marie Skłodowska-Curie Actions, National Science Foundation Graduate Research Fellowship Program
OpenAlex ID: W7166093519
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