{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:03:23Z","timestamp":1789988603301,"version":"4.0.1"},"reference-count":87,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470912"],"award-info":[{"award-number":["32470912"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32370917"],"award-info":[{"award-number":["32370917"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Obesity is a major risk factor for male infertility; however, how different obesity etiologies reshape testicular cellular states and transcriptional programs remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to characterize cell\u2010type\u2010specific transcriptional alterations associated with testicular dysfunction in dietary and genetic obesity models using single\u2010cell RNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Normal diet (ND) mice served as controls, whereas high\u2010fat diet (HFD) and leptin\u2010deficient obese (OB) mice represented diet\u2010induced and genetic obesity models, respectively. Testicular phenotypes were evaluated, and single\u2010cell RNA sequencing was performed to characterize obesity\u2010associated changes in cellular composition, developmental trajectories, transcriptional programs, inferred metabolic activity, and regulatory networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Both HFD and OB mice exhibited impaired reproductive phenotypes, accompanied by alterations in testicular cellular composition. Single\u2010cell analysis revealed increased proportions of early germ\u2010cell populations and reduced mature spermatid populations in obese testes. Spermatocytes showed the most prominent transcriptional alterations, characterized by disrupted developmental trajectories, enhanced stress\u2010 and metabolism\u2010associated programs, and altered expression of genes involved in meiotic progression and DNA damage responses. Increased RAD51 accumulation further indicated activation of meiotic DNA damage response pathways in obese testes. In addition, somatic populations, including Leydig cells, Sertoli cells, and immune cells, exhibited altered metabolic and endocrine\u2010related transcriptional programs. Although both obesity models shared common transcriptional changes, OB mice displayed broader alterations involving mitochondrial, steroidogenic, and developmental programs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings reveal that obesity\u2010associated testicular dysfunction involves coordinated alterations in germ\u2010cell developmental programs and somatic\u2010cell metabolic states. The distinct transcriptional responses between dietary and genetic obesity highlight how obesity etiology shapes cellular alterations within the testicular microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides a single\u2010cell framework for understanding how different obesity states affect testicular cellular organization and transcriptional regulation, providing insights into the cellular and transcriptional basis of obesity\u2010associated impairment of spermatogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70378","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:40:50Z","timestamp":1789987250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dissection of Obesity\u2010Induced Spermatogenic Dysfunction 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