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University","award":["2023KYQD0013"],"award-info":[{"award-number":["2023KYQD0013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>With industrial development, endocrine-disrupting chemicals have continued to accumulate in the environment, attracting growing attention due to their potential effects on biological health. The reproductive toxicity of diethylstilbestrol (DES), a synthetic estrogen widely present in the environment, is widely documented; however, studies on its effects on the immune system remain limited. In this study, adult male golden hamsters were subcutaneously administered varying doses of DES (0, 0.01, 0.1, and 1.0 mg\/kg) for seven consecutive days to assess its immunomodulatory impact on peripheral blood and the spleen. We found that the DES treatment significantly reduced spleen index, white pulp area, and splenic lymphocyte proliferation while increasing caspase-3-positive apoptotic cells and inducible nitric oxide synthase expression. In peripheral blood, DES induced a dose-dependent suppression of lymphocyte proliferation, with lipopolysaccharide- and concanavalin A-stimulated proliferation reduced by 47.68\u201371.76% and 44.23\u201372.7%, respectively. Concurrently, DES significantly downregulated the pro-inflammatory cytokines IL-2 and IFN-\u03b3 (p &lt; 0.01) while upregulating the anti-inflammatory cytokines IL-4 and IL-10 (p &lt; 0.01). Furthermore, DES treatment impaired antioxidant defenses, decreasing the activity of superoxide dismutase, glutathione peroxidase, and catalase while elevating malondialdehyde levels. Notably, DES led to the upregulation of G protein-coupled estrogen receptor and estrogen receptor \u03b1 at both transcriptional and protein levels, whereas estrogen receptor \u03b2 mRNA expression increased despite a decline in protein levels. This study provides critical experimental evidence elucidating the immunoregulatory effects of endocrine-disrupting environmental estrogens.<\/jats:p>","DOI":"10.3390\/toxics13050397","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T07:46:49Z","timestamp":1747295209000},"page":"397","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Diethylstilbestrol on the Structure and Function of the Spleen in Male Golden Hamsters"],"prefix":"10.3390","volume":"13","author":[{"given":"Jian","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Embryo Development and Reproductive Regulation Anhui Province, College of Biology and Food Engineering, Fuyang Normal University, Fuyang 236037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiping","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy of Domestic Animals, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy of Domestic Animals, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy of Domestic Animals, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhua","family":"Su","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Yunnan Agricultural University, Panlong, Kunming 650201, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2576-5977","authenticated-orcid":false,"given":"Yaoxing","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy of Domestic Animals, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9425-9982","authenticated-orcid":false,"given":"Jing","family":"Cao","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy of Domestic Animals, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41574-019-0273-8","article-title":"Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification","volume":"16","author":"Vandenberg","year":"2020","journal-title":"Nat. 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