{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:40:54Z","timestamp":1791895254564,"version":"4.3.4"},"reference-count":65,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:00:00Z","timestamp":1566172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81660255, No. 81360098 and No. 21777036"],"award-info":[{"award-number":["No. 81660255, No. 81360098 and No. 21777036"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Young Scientist Training Project of Jiangxi Province, China","award":["No. 20153BCB23032"],"award-info":[{"award-number":["No. 20153BCB23032"]}]},{"name":"the Research fund for postgraduate program of Nanchang University","award":["No. cx2015179"],"award-info":[{"award-number":["No. cx2015179"]}]},{"name":"the Youth Plan of Beijing Academy of Science and Technology","award":["YC201809"],"award-info":[{"award-number":["YC201809"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Zinc oxide nanoparticles (ZnO NPs) have shown adverse health impact on the human male reproductive system, with evidence of inducing apoptosis. However, whether or not ZnO NPs could promote autophagy, and the possible role of autophagy in the progress of apoptosis, remain unclear. In the current study, in vitro and in vivo toxicological responses of ZnO NPs were explored by using a mouse model and mouse Leydig cell line. It was found that intragastrical exposure of ZnO NPs to mice for 28 days at the concentrations of 100, 200, and 400 mg\/kg\/day disrupted the seminiferous epithelium of the testis and decreased the sperm density in the epididymis. Furthermore, serum testosterone levels were markedly reduced. The induction of apoptosis and autophagy in the testis tissues was disclosed by up-regulating the protein levels of cleaved Caspase-8, cleaved Caspase-3, Bax, LC3-II, Atg 5, and Beclin 1, accompanied by down-regulation of Bcl 2. In vitro tests showed that ZnO NPs could induce apoptosis and autophagy with the generation of oxidative stress. Specific inhibition of autophagy pathway significantly decreased the cell viability and up-regulated the apoptosis level in mouse Leydig TM3 cells. In summary, ZnO NPs can induce apoptosis and autophagy via oxidative stress, and autophagy might play a protective role in ZnO NPs-induced apoptosis of mouse Leydig cells.<\/jats:p>","DOI":"10.3390\/ijms20164042","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T06:10:14Z","timestamp":1566195014000},"page":"4042","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Role of Autophagy in Zinc Oxide Nanoparticles-Induced Apoptosis of Mouse LEYDIG Cells"],"prefix":"10.3390","volume":"20","author":[{"given":"Jingcao","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingfan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Occupational Health and Safety, Beijing Municipal Institute of Labor Protection, Beijing 100054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Occupational Health and Safety, Beijing Municipal Institute of Labor Protection, Beijing 100054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichuan","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Occupational Health and Safety, Beijing Municipal Institute of Labor Protection, Beijing 100054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Aerospace, Mechanical and Manufacturing Engineering, RMIT University, Bundoora, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6488-6133","authenticated-orcid":false,"given":"Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Occupational Health and Safety, Beijing Municipal Institute of Labor Protection, Beijing 100054, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0756-1647","authenticated-orcid":false,"given":"Jiaxiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Nanchang 330006, China"},{"name":"Jiangxi Provincial Key Laboratory of Reproductive Physiology and Pathology, Nanchang 330006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1002\/tox.22159","article-title":"Review: Morphofunctional and biochemical markers of stress in sea urchin life stages exposed to engineered nanoparticles","volume":"31","author":"Gambardella","year":"2016","journal-title":"Environ. 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