{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:38:29Z","timestamp":1791221909414,"version":"4.1.0"},"reference-count":47,"publisher":"Portland Press Ltd.","issue":"8","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,4,30]]},"abstract":"<jats:p>Recent studies have suggested a role for abdominal obesity in male infertility. Previous studies have found that cell apoptosis exerts an important role in obesity-related male infertility. C1q\/TNF-related protein 3 (CTRP3), a paralog of adiponectin, has been proposed to exert anti-apoptotic effects and to attenuate diabetes-related cardiac injuries. However, the role of CTRP3 in high-fat diet (HFD)-induced spermatogenic impairment remains unclear. In the present study, we fed male mice an HFD for 24 weeks to induce obesity. The expression of CTRP3 was decreased by HFD feeding. Supplementation with the recombinant human globular domain of CTRP3 (0.25 \u03bcg\/g\/day) for 4 weeks beginning at 20 weeks of the HFD improved spermatogenic function in the HFD-fed mice, which were characterized by improved testis morphology, increased testis weight\/body weight ratio, and increased sperm count, sperm viability, and sperm motility. We also found that CTRP3 infusion resulted in the attenuation of endoplasmic reticulum (ER) stress and the activation of silence information regulator 1 (SIRT1) in the testes of obese mice. Our in vitro study also suggested that CTRP3 attenuated the palmitic acid (PA)-induced reductions in sperm viability and motility via the inhibition of ER stress. Moreover, germ cell-specific Sirtuin1 knockout abolished the protective effects of CTRP3 in vivo and in vitro. In vitro studies of human sperm showed that the protective effects of CTRP3 on sperm viability and motility were abrogated by a specific inhibitor of SIRT1. Thus, our results demonstrated that CTRP3 expression protected against HFD-induced spermatogenic deficiency through the SIRT1\/ER stress pathway.<\/jats:p>","DOI":"10.1042\/cs20180179","type":"journal-article","created":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T16:40:44Z","timestamp":1521823244000},"page":"883-899","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["CTRP3 attenuates high-fat diet-induced male reproductive dysfunction in mice"],"prefix":"10.1042","volume":"132","author":[{"given":"Yang","family":"Mu","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, Renmin Hospital of Wuhan University, Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai-lang","family":"Yin","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Renmin Hospital of Wuhan University, Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yin","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Renmin Hospital of Wuhan University, Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Hu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Renmin Hospital of Wuhan University, Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Renmin Hospital of Wuhan University, Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,4,30]]},"reference":[{"key":"2021113011002155000_B1","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/j.fertnstert.2008.10.049","article-title":"Infertility service use among U.S. women: 1995 and 2002","volume":"93","author":"Chandra","year":"2010","journal-title":"Fertil. Steril."},{"key":"2021113011002155000_B2","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.eururo.2011.10.001","article-title":"European Association of Urology guidelines on vasectomy","volume":"61","author":"Dohle","year":"2012","journal-title":"Eur. Urol."},{"key":"2021113011002155000_B3","doi-asserted-by":"publisher","first-page":"619","DOI":"10.2164\/jandrol.106.000125","article-title":"Obesity and male reproductive potential","volume":"27","author":"Hammoud","year":"2006","journal-title":"J. Androl."},{"key":"2021113011002155000_B4","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.fertnstert.2004.03.056","article-title":"Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men","volume":"82","author":"Jensen","year":"2004","journal-title":"Fertil. Steril."},{"key":"2021113011002155000_B5","doi-asserted-by":"publisher","first-page":"3178","DOI":"10.1093\/humrep\/det379","article-title":"Body mass index in relation to semen quality and reproductive hormones in New Zealand men: a cross-sectional study in fertility clinics","volume":"28","author":"Macdonald","year":"2013","journal-title":"Hum. Reprod."},{"key":"2021113011002155000_B6","doi-asserted-by":"publisher","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":"2021113011002155000_B7","doi-asserted-by":"publisher","first-page":"3588","DOI":"10.3892\/mmr.2016.5712","article-title":"Curcumin ameliorates highfat dietinduced spermatogenesis dysfunction","volume":"14","author":"Mu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"2021113011002155000_B8","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1007\/s10815-015-0506-2","article-title":"Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet","volume":"32","author":"Yan","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"2021113011002155000_B9","first-page":"857516","article-title":"Endoplasmic reticulum stress: its role in disease and novel prospects for therapy","volume":"2012","author":"Schonthal","year":"2012","journal-title":"Scientifica (Cairo)"},{"key":"2021113011002155000_B10","doi-asserted-by":"publisher","first-page":"518","DOI":"10.2337\/db08-1746","article-title":"Endoplasmic reticulum stress: another link between obesity and insulin resistance\/inflammation?","volume":"58","author":"Boden","year":"2009","journal-title":"Diabetes"},{"key":"2021113011002155000_B11","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3389\/fncel.2014.00213","article-title":"A molecular web: endoplasmic reticulum stress, inflammation, and oxidative stress","volume":"8","author":"Chaudhari","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"2021113011002155000_B12","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/nature17041","article-title":"Protein misfolding in the endoplasmic reticulum as a conduit to human disease","volume":"529","author":"Wang","year":"2016","journal-title":"Nature"},{"key":"2021113011002155000_B13","doi-asserted-by":"publisher","first-page":"C582","DOI":"10.1152\/ajpcell.00258.2014","article-title":"Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 1. An overview","volume":"307","author":"Dufey","year":"2014","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2021113011002155000_B14","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1146\/annurev-pathol-012513-104649","article-title":"The role of endoplasmic reticulum stress in human pathology","volume":"10","author":"Oakes","year":"2015","journal-title":"Annu. Rev. Pathol."},{"key":"2021113011002155000_B15","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1038\/ijo.2017.203","article-title":"Diet-induced obesity leads to metabolic dysregulation in offspring via endoplasmic reticulum stress in a sex-specific manner","volume":"2","author":"Park","year":"2017","journal-title":"Int. J. Obes. (Lond.)"},{"key":"2021113011002155000_B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2017.08.001","article-title":"Astrocytes and endoplasmic reticulum stress: a bridge between obesity and neurodegenerative diseases","author":"Martin-Jimenez","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"2021113011002155000_B17","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1042\/BJ20101293","article-title":"Regulation of unfolded protein response modulator XBP1s by acetylation and deacetylation","volume":"433","author":"Wang","year":"2011","journal-title":"Biochem. J."},{"key":"2021113011002155000_B18","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.exphem.2011.06.007","article-title":"Resveratrol triggers the pro-apoptotic endoplasmic reticulum stress response and represses pro-survival XBP1 signaling in human multiple myeloma cells","volume":"39","author":"Wang","year":"2011","journal-title":"Exp. Hematol."},{"key":"2021113011002155000_B19","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/srep00150","article-title":"SIRT1 associates with eIF2-alpha and regulates the cellular stress response","volume":"1","author":"Ghosh","year":"2011","journal-title":"Sci. Rep."},{"key":"2021113011002155000_B20","doi-asserted-by":"publisher","first-page":"39691","DOI":"10.1074\/jbc.M110.180695","article-title":"C1q\/TNF-related protein-3 (CTRP3), a novel adipokine that regulates hepatic glucose output","volume":"285","author":"Peterson","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2021113011002155000_B21","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1007\/s00125-017-4232-4","article-title":"CTRP3 attenuates cardiac dysfunction, inflammation, oxidative stress and cell death in diabetic cardiomyopathy in rats","volume":"60","author":"Ma","year":"2017","journal-title":"Diabetologia"},{"key":"2021113011002155000_B22","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1159\/000446353","article-title":"Complement-C1q TNF-related protein 3 alleviates mesangial cell activation and inflammatory response stimulated by secretory IgA","volume":"43","author":"Zhang","year":"2016","journal-title":"Am. J. Nephrol."},{"key":"2021113011002155000_B23","doi-asserted-by":"publisher","first-page":"3159","DOI":"10.1161\/CIRCULATIONAHA.112.099937","article-title":"C1q\/tumor necrosis factor-related protein-3, a newly identified adipokine, is a novel antiapoptotic, proangiogenic, and cardioprotective molecule in the ischemic mouse heart","volume":"125","author":"Yi","year":"2012","journal-title":"Circulation"},{"key":"2021113011002155000_B24","doi-asserted-by":"publisher","first-page":"10302","DOI":"10.1073\/pnas.0403760101","article-title":"A family of Acrp30\/adiponectin structural and functional paralogs","volume":"101","author":"Wong","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011002155000_B25","doi-asserted-by":"publisher","first-page":"e133955","DOI":"10.1371\/journal.pone.0133955","article-title":"Lower circulating C1q\/TNF-related protein-3 (CTRP3) levels are associated with obesity: a cross-sectional study","volume":"10","author":"Wolf","year":"2015","journal-title":"PLoS ONE"},{"key":"2021113011002155000_B26","doi-asserted-by":"publisher","first-page":"3085","DOI":"10.1016\/j.bbagen.2016.10.022","article-title":"Globular CTRP3 promotes mitochondrial biogenesis in cardiomyocytes through AMPK\/PGC-1alpha pathway","volume":"1861","author":"Zhang","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"2021113011002155000_B27","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1002\/(SICI)1526-968X(200002)26:2%3c116::AID-GENE4%3e3.0.CO;2-X","article-title":"Targeted insertion of Cre recombinase into the TNAP gene: excision in primordial germ cells","volume":"26","author":"Lomeli","year":"2000","journal-title":"Genesis"},{"key":"2021113011002155000_B28","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/cr.2014.70","article-title":"Atg7 is required for acrosome biogenesis during spermatogenesis in mice","volume":"24","author":"Wang","year":"2014","journal-title":"Cell Res."},{"key":"2021113011002155000_B29","doi-asserted-by":"publisher","first-page":"43475","DOI":"10.1038\/srep43475","article-title":"Diet-induced obesity impairs spermatogenesis: a potential role for autophagy","volume":"7","author":"Mu","year":"2017","journal-title":"Sci. Rep."},{"key":"2021113011002155000_B30","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1093\/cvr\/cvt232","article-title":"Toll-interacting protein (Tollip) negatively regulates pressure overload-induced ventricular hypertrophy in mice","volume":"101","author":"Liu","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"2021113011002155000_B31","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"2021113011002155000_B32","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1095\/biolreprod.109.078915","article-title":"Diet-induced obesity in male mice is associated with reduced fertility and potentiation of acrylamide-induced reproductive toxicity","volume":"82","author":"Ghanayem","year":"2010","journal-title":"Biol. Reprod."},{"key":"2021113011002155000_B33","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.pestbp.2014.01.002","article-title":"Antioxidant mediated ameliorative steroidogenesis by Commelina benghalensis L. and Cissus quadrangularis L. against quinalphos induced male reproductive toxicity","volume":"109","author":"Kokilavani","year":"2014","journal-title":"Pestic. Biochem. Physiol."},{"key":"2021113011002155000_B34","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1007\/s10815-014-0191-6","article-title":"The long-term effects of superovulation on fertility and sexual behavior of male offspring in mice","volume":"31","author":"Wei","year":"2014","journal-title":"J. Assist. Reprod. Genet."},{"key":"2021113011002155000_B35","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.cyto.2012.01.018","article-title":"The adiponectin paralog C1q\/TNF-related protein 3 (CTRP3) stimulates testosterone production through the cAMP\/PKA signaling pathway","volume":"58","author":"Otani","year":"2012","journal-title":"Cytokine"},{"key":"2021113011002155000_B36","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.fertnstert.2013.09.001","article-title":"Cigarette smoking is associated with abnormal histone-to-protamine transition in human sperm","volume":"101","author":"Yu","year":"2014","journal-title":"Fertil. Steril."},{"key":"2021113011002155000_B37","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1016\/j.cell.2007.04.027","article-title":"ER stress triggers apoptosis by activating BH3-only protein Bim","volume":"129","author":"Puthalakath","year":"2007","journal-title":"Cell"},{"key":"2021113011002155000_B38","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1093\/abbs\/gmu048","article-title":"New insights into the roles of CHOP-induced apoptosis in ER stress","volume":"46","author":"Li","year":"2014","journal-title":"Acta Biochim. Biophys. Sin. (Shanghai)"},{"key":"2021113011002155000_B39","doi-asserted-by":"publisher","first-page":"16013","DOI":"10.1038\/srep16013","article-title":"Inhibition of HMGB1 release via salvianolic acid B-mediated SIRT1 up-regulation protects rats against non-alcoholic fatty liver disease","volume":"5","author":"Zeng","year":"2015","journal-title":"Sci. Rep."},{"key":"2021113011002155000_B40","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1161\/CIRCRESAHA.116.304707","article-title":"MicroRNA-451 exacerbates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy in mice through suppression of the LKB1\/AMPK pathway","volume":"116","author":"Kuwabara","year":"2015","journal-title":"Circ. Res."},{"key":"2021113011002155000_B41","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s13098-015-0029-0","article-title":"Serum C1q\/TNF-related protein-3 (CTRP3) levels are decreased in obesity and hypertension and are negatively correlated with parameters of insulin resistance","volume":"7","author":"Deng","year":"2015","journal-title":"Diabetol. Metab. Syndr."},{"key":"2021113011002155000_B42","doi-asserted-by":"publisher","first-page":"E332","DOI":"10.1152\/ajpendo.00248.2015","article-title":"CTRP3 deficiency reduces liver size and alters IL-6 and TGFbeta levels in obese mice","volume":"310","author":"Wolf","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"2021113011002155000_B43","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.chemosphere.2017.09.082","article-title":"The reproductive toxicology of male SD rats after PM2.5 exposure mediated by the stimulation of endoplasmic reticulum stress","volume":"189","author":"Liu","year":"2017","journal-title":"Chemosphere"},{"key":"2021113011002155000_B44","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/aja.2012.129","article-title":"N-acetylcysteine protects against cadmium-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in testes","volume":"15","author":"Ji","year":"2013","journal-title":"Asian J. Androl."},{"key":"2021113011002155000_B45","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2017.1972","article-title":"Berberine improves diabetic encephalopathy through the SIRT1\/ER stress pathway in db\/db mice","author":"Li","year":"2017","journal-title":"Rejuvenation Res."},{"key":"2021113011002155000_B46","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1080\/10715762.2017.1351027","article-title":"Hydrogen alleviates hyperoxic acute lung injury related endoplasmic reticulum stress in rats through upregulation of SIRT1","volume":"51","author":"Sun","year":"2017","journal-title":"Free Radic. Res."},{"key":"2021113011002155000_B47","doi-asserted-by":"publisher","first-page":"3587","DOI":"10.3892\/mmr.2017.7004","article-title":"Hydrogen sulfide prevents homocysteineinduced endoplasmic reticulum stress in PC12 cells by upregulating SIRT1","volume":"16","author":"Wang","year":"2017","journal-title":"Mol. Med. Rep."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/132\/8\/883\/446633\/cs-2018-0179.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/132\/8\/883\/446633\/cs-2018-0179.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T11:52:46Z","timestamp":1638273166000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/132\/8\/883\/72040\/CTRP3-attenuates-high-fat-diet-induced-male"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,30]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2018,4,30]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20180179","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,30]]}}}