{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:05:25Z","timestamp":1788455125900,"version":"build-2803163510"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"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":["81773466"],"award-info":[{"award-number":["81773466"]}],"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":["82204082"],"award-info":[{"award-number":["82204082"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Ferroptosis hallmarked by lipid peroxidation and iron homeostasis imbalance is involved in the occurrence and development of various diseases. The plant growth regulator chlormequat chloride (CCC) can contribute to the causality and exacerbation of reproductive disorders. However, the mechanism by which CCC may cause Leydig cell attenuation remains poorly understood. In this study, TM3 Leydig cells were used to investigate the inhibitory effect of CCC on cell growth and its possible mechanism. The results showed that CCC caused apoptosis, pyroptosis, ferroptosis and necroinflammation in TM3 cells. By comparing the effects of ferroptosis inhibitor Ferrostatin-1 (Fer-1) and pan-Caspase inhibitor Z-VAD-FMK (ZVF) on lipid peroxidation and Caspase-mediated regulated cell death (RCD), we found that Fer-1 was better at rescuing the growth of TM3 cells than ZVF. Although ZVF reduced mitochondrial ROS level and inhibited the activation of Caspase3 and Caspase1, it could not significantly ameliorate lipid peroxidation and the levels of IL-1\u03b2 and HMGB1 like Fer-1. Therefore, ferroptosis might be a key non apoptotic RCD mode responsible for CCC-driven inflammation, leading to weakened viability and proliferation of TM3 cells. In addition, overexpression of ferritin light chain (FTL) promoted the resistance of TM3 cells to CCC-induced ferroptosis-mediated inflammation and to some extent improved the inhibition of viability and proliferation. Altogether, ferroptosis-initiated inflammation might play a key role in CCC-impaired TM3 cell growth.<\/jats:p>","DOI":"10.3390\/cells13110979","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T03:49:28Z","timestamp":1717559368000},"page":"979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Chlormequat Chloride Inhibits TM3 Leydig Cell Growth via Ferroptosis-Initiated Inflammation"],"prefix":"10.3390","volume":"13","author":[{"given":"Xiaoxia","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenping","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8685-8664","authenticated-orcid":false,"given":"Wanqian","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Peking University, Beijing 100191, China"},{"name":"Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"ref_1","first-page":"18","article-title":"Influence of Chlormequat Chloride on the Formation of a Photosynthetic Apparatus and Productivity of Linseed","volume":"6","author":"Olena","year":"2018","journal-title":"Sci. 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