{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:24:06Z","timestamp":1780406646035,"version":"3.54.1"},"reference-count":57,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["2023"],"award-info":[{"award-number":["2023"]}],"id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Background: Obesity, a chronic metabolic disorder, is related to cardiovascular diseases, diabetes, cancer, and reproductive disorders. The relationship between obesity and male infertility is now well recognized, but the mechanisms involved are unclear. We aimed to observe the effect of obesity on spermatogenesis and to investigate the role of histone ubiquitination and acetylation modifications in obesity-induced spermatogenesis disorders. Methods: Thirty male C57BL\/6J mice were randomly divided into two groups. The control group was fed with a general maintenance diet (12% fat), while a high-fat diet (HFD) group was fed with 40% fat for 10 weeks; then, they were mated with normal females. The fertility of male mice was calculated, testicular and sperm morphology were observed, and the expression levels of key genes and the levels of histone acetylation and ubiquitination modification during spermatogenesis were detected. Results: The number of sperm was decreased, as well as the sperm motility, while the number of sperm with malformations was increased. In the testes, the mRNA and protein expression levels of gonadotropin-regulated testicular RNA helicase (GRTH\/DDX25), chromosome region maintenance-1 protein (CRM1), high-mobility group B2 (HMGB2), phosphoglycerate kinase 2 (PGK2), and testicular angiotensin-converting enzyme (tACE) were decreased. Furthermore, obesity led to a decrease in ubiquitinated H2A (ubH2A) and reduced levels of histone H3 acetylation K18 (H3AcK18) and histone H4 acetylation K5, K8, K12, and K16 (H4tetraAck), which disrupted protamine 1 (Prm1) deposition in testis tissue. Conclusion: These results suggest that low levels of histone ubiquitination and acetylation are linked with obesity-induced disorders during spermatogenesis, contributing to a better understanding of obesity-induced damage to male reproduction.<\/jats:p>","DOI":"10.3390\/toxics12040296","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T08:22:44Z","timestamp":1713342164000},"page":"296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Decreased Ubiquitination and Acetylation of Histones 3 and 4 Are Associated with Obesity-Induced Disorders of Spermatogenesis in Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8196-7402","authenticated-orcid":false,"given":"Mahamadou","family":"Fofana","sequence":"first","affiliation":[{"name":"Center for Global Health, China International Cooperation Center for Environment and Human Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyang","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Global Health, China International Cooperation Center for Environment and Human Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Global Health, China International Cooperation Center for Environment and Human Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Global Health, China International Cooperation Center for Environment and Human Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wu","sequence":"additional","affiliation":[{"name":"Suzhou Center for Disease Control and Prevention, Suzhou Institute for Advanced Study of Public Health, Suzhou School, Nanjing Medical University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Animal Core Facility, The Key Laboratory of Model Animal, Jiangsu Animal Experimental Center for Medical and Pharmaceutical Research, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qizhan","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Global Health, China International Cooperation Center for Environment and Human Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China"},{"name":"Suzhou Center for Disease Control and Prevention, Suzhou Institute for Advanced Study of Public Health, Suzhou School, Nanjing Medical University, Suzhou 215004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R123","DOI":"10.1530\/REP-17-0161","article-title":"Obesity, a serious etiologic factor for male subfertility in modern society","volume":"154","author":"Liu","year":"2017","journal-title":"Reproduction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1210\/en.2018-00569","article-title":"Genetically Inherited Obesity and High-Fat Diet-Induced Obesity Differentially Alter Spermatogenesis in Adult Male Rats","volume":"160","author":"Deshpande","year":"2019","journal-title":"Endocrinology"},{"key":"ref_3","first-page":"R2","article-title":"High body-mass index\u2014Level 2 risk","volume":"393","author":"Dieases","year":"2020","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S0140-6736(23)02750-2","article-title":"Worldwide trends in underweight and obesity from 1990 to 2022: A pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults","volume":"403","author":"Phelps","year":"2024","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3109\/14647273.2015.1070438","article-title":"Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility","volume":"18","author":"Davidson","year":"2015","journal-title":"Hum. 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