{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:01:17Z","timestamp":1777975277262,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071632"],"award-info":[{"award-number":["82071632"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["W0069"],"award-info":[{"award-number":["W0069"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Program for Youth Innovation in Future Medicine, Chongqing Medical University","award":["82071632"],"award-info":[{"award-number":["82071632"]}]},{"name":"Program for Youth Innovation in Future Medicine, Chongqing Medical University","award":["W0069"],"award-info":[{"award-number":["W0069"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Difenoconazole (DFZ) is a broad-spectrum triazole fungicide that is widely utilized in agriculture. Although DFZ has been demonstrated to induce reproductive toxicity in aquatic species, its toxic effects on the mammalian reproductive system have yet to be fully elucidated. In vivo, male mice were administered 0, 20 or 40 mg\/kg\/d of DFZ via oral gavage for 35 days. Consequently, DFZ significantly decreased testicular organ coefficient, sperm count and testosterone levels, augmented sperm malformation rates, and elicited histopathological alterations in testes. TUNEL assay showed increased apoptosis in testis. Western blotting results suggested abnormally high expression of the sperm meiosis-associated proteins STRA8 and SCP3. The concentrations of retinoic acid (RA), retinaldehyde (RE), and retinol (ROL) were increased in the testicular tissues of DFZ-treated groups. The mRNA expression level of genes implicated in RA synthesis significantly increased while genes involved in RA catabolism significantly decreased. In vitro, DFZ reduced cell viability and increased RA, RE, and ROL levels in GC-2 cells. Transcriptome analysis revealed a significant enrichment of numerous terms associated with the RA pathway and apoptosis. The qPCR experiment verified the transcriptome results. In conclusion, our results indicate that DFZ exposure can disrupt RA signaling pathway homeostasis, and induce testicular injury in mice testes.<\/jats:p>","DOI":"10.3390\/toxics11040328","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T04:45:35Z","timestamp":1680151535000},"page":"328","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Difenoconazole Exposure Induces Retinoic Acid Signaling Dysregulation and Testicular Injury in Mice Testes"],"prefix":"10.3390","volume":"11","author":[{"given":"Xiangqin","family":"Zheng","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuexin","family":"Wei","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiadong","family":"Chen","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinggang","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengjun","family":"Yu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-8615","authenticated-orcid":false,"given":"Yifan","family":"Hong","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianju","family":"Shen","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunlan","family":"Long","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanghui","family":"Wei","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0083-561X","authenticated-orcid":false,"given":"Shengde","family":"Wu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing 400014, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"ref_1","first-page":"494","article-title":"Toxicity of an imidazoline (or glyoxalidine) fungicide","volume":"4","author":"Carpenter","year":"1951","journal-title":"A.M.A. Arch. 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