{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T16:29:02Z","timestamp":1782750542830,"version":"3.54.5"},"reference-count":145,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fujian Provincial Natural Science Foundation","award":["2022J01172"],"award-info":[{"award-number":["2022J01172"]}]},{"name":"Fujian Provincial Natural Science Foundation","award":["2024J01458"],"award-info":[{"award-number":["2024J01458"]}]},{"name":"Fujian Provincial Natural Science Foundation","award":["2022G028"],"award-info":[{"award-number":["2022G028"]}]},{"name":"Key Projects of Scientific and Technological Innovation in Fujian Province","award":["2022J01172"],"award-info":[{"award-number":["2022J01172"]}]},{"name":"Key Projects of Scientific and Technological Innovation in Fujian Province","award":["2024J01458"],"award-info":[{"award-number":["2024J01458"]}]},{"name":"Key Projects of Scientific and Technological Innovation in Fujian Province","award":["2022G028"],"award-info":[{"award-number":["2022G028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Diabetes mellitus, as a metabolic disorder, has received growing attention for its detrimental effects on the male reproductive system (particularly the testes) manifesting as increased oxidative stress, reduced blood perfusion, heightened inflammation, and germ cell apoptosis under hyperglycemic conditions. Hypoxia-inducible factor (HIF)-1\u03b1, a pivotal transcription factor in cellular hypoxia responses, plays a crucial role in regulating metabolism, angiogenesis, and apoptosis. Emerging evidence underscores its significant physiological and pathological roles in diabetic testicular injury. This review outlines the structural domains, activation mechanisms, and key target genes of HIF-1\u03b1, and further examines its involvement in diabetes-induced oxidative stress, impaired perfusion, endocrine dysregulation, and the imbalance of apoptosis and autophagy in testicular tissue. Notably, HIF-1\u03b1 exerts protective effects by activating canonical signaling pathways such as phosphoinositide-3 kinase (PI-3K)\/protein kinase B (Akt), mitogen-activated protein kinase (MAPK)\/extracellular signal-regulated kinase (ERK), and nuclear factor (NF)-\u03baB, thereby enhancing antioxidant gene expression, promoting angiogenesis, and upregulating anti-apoptotic proteins. Furthermore, HIF-1\u03b1 may help stabilize androgen levels by preserving Leydig cell function, potentially alleviating diabetes-associated gonadal dysfunction. This review also discusses the feasibility of targeting HIF-1\u03b1 as a novel therapeutic strategy. In conclusion, a comprehensive understanding of HIF-1\u03b1\u2019s mechanistic role in diabetic testicular damage provides valuable insights into the pathogenesis of diabetes-related reproductive disorders and offers new avenues for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/biom15081190","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T10:59:01Z","timestamp":1755601141000},"page":"1190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Contribution and Regulation of HIF-1\u03b1 in Testicular Injury Induced by Diabetes Mellitus"],"prefix":"10.3390","volume":"15","author":[{"given":"Defan","family":"Wang","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4309-0221","authenticated-orcid":false,"given":"Zhenghong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou 350007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renfeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, School of Medicine, Xiamen University, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-9630","authenticated-orcid":false,"given":"Zhengchao","family":"Wang","sequence":"additional","affiliation":[{"name":"Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou 350007, China"},{"name":"Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","first-page":"e18300","article-title":"A new hope in type 2 diabetes mellitus management: Sodium-glucose cotransporter 2 inhibitors","volume":"13","author":"Chaurasia","year":"2021","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/B978-0-444-53480-4.00015-1","article-title":"General aspects of diabetes mellitus","volume":"126","author":"Alam","year":"2014","journal-title":"Handb. 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