{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:37:30Z","timestamp":1760060250296,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Beijing Municipality","award":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"],"award-info":[{"award-number":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"]}]},{"name":"National Natural Science Foundation of China","award":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"],"award-info":[{"award-number":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"]}]},{"name":"Open Project of the Key Laboratory of Higher Education in Inner Mongolia Autonomous Region for Animal Embryo and Development Engineering","award":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"],"award-info":[{"award-number":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"]}]},{"name":"Biological and Medical Sciences of Applied Summit Nurturing Disciplines in Anhui Province","award":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"],"award-info":[{"award-number":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"]}]},{"name":"Key projects of natural science research projects in Anhui universities","award":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"],"award-info":[{"award-number":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"]}]},{"name":"Scientific research project of Fuyang Normal University","award":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"],"award-info":[{"award-number":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"]}]},{"name":"Technical Service Contract Between Shenzhen Mairuide Technology Co., Ltd. and Fuyang Normal University","award":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"],"award-info":[{"award-number":["6242017","6192012","31972632","31572474","[2023]13","2022AH051345","2023KYQD0013","HX2023021000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Due to the growing environmental burden of endocrine-disrupting chemicals (EDCs), there is an increasing concern regarding the reproductive hazards posed by synthetic estrogens, particularly diethylstilbestrol (DES). However, the precise mechanisms by which DES disrupts uterine endocrine function and immune homeostasis leading to pregnancy failure remain unclear. Given that wild rodents serve as key reservoirs for zoonotic diseases such as plague, reproductive interventions targeting their pregnancy processes hold significant ecological implications for disease control. In this study, female mice in estrus were randomly divided into four experimental groups, receiving DES at doses of 0 (control), 0.02 (low), 0.2 (medium), and 2 mg\/kg (high), respectively. For five consecutive days, mice were injected subcutaneously on a daily basis, with the goal of examining DES-related alterations in hormone secretion and local immune responses within the uterus and spleen. It was found that high-dose DES treatment significantly increased maternal body weight and spleen weight during early pregnancy (p &lt; 0.05). Meanwhile, reproductive function declined progressively with increasing doses, as indicated by decreased ovarian and uterine weights, fewer embryos, and extended estrous cycle duration (p &lt; 0.05). Hematoxylin and eosin staining revealed that high-dose DES markedly reduced uterine gland density at day P5, accompanied by epithelial vacuolar degeneration and nuclear pyknosis. The proportion of uterine glands relative to total uterine area also decreased significantly with increasing DES doses. Moreover, DES inhibited lymphocyte proliferation in both the uterus and spleen in a dose-dependent fashion, with ConA- and LPS-induced proliferation rates decreasing by 0.78\u201330.70% and 1.91\u201318.20%, respectively (p &lt; 0.05). The proinflammatory cytokine IL-2 was significantly elevated by DES, whereas the anti-inflammatory cytokine IL-4 showed a notable decrease (p &lt; 0.05). DES administration notably decreased uterine expression of proliferating cell nuclear antigen. In contrast, the numbers of B-cell lymphoma 2- and Bcl-2-associated X protein-positive cells rose, along with upregulated levels of inducible nitric oxide synthase. Furthermore, DES impaired antioxidant defenses in both the uterus and spleen, evidenced by the decreased activities of superoxide dismutase and glutathione peroxidase, reduced total antioxidant capacity, and elevated malondialdehyde levels. This study elucidates the multifaceted mechanisms by which DES impairs the early gestational reproductive environment, filling a critical knowledge gap regarding its interference with the uterus\u2013immune axis, and expands the current understanding of the ecotoxicological impacts of endocrine-disrupting chemicals.<\/jats:p>","DOI":"10.3390\/toxics13080672","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T09:59:13Z","timestamp":1754906353000},"page":"672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Diethylstilbestrol on Uterus Structure and Immunological Function in Mice During Early Pregnancy"],"prefix":"10.3390","volume":"13","author":[{"given":"Jian","family":"Li","sequence":"first","affiliation":[{"name":"Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, College of Biology and Food Engineering, Fuyang Normal University, Yingzhou, Fuyang 236037, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiping","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy of Domestic Animals, State 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":"Guan","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Anatomy of Domestic Animals, State 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, State 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, State 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":[[2025,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1111\/1749-4877.12511","article-title":"Plague reservoir species throughout the world","volume":"16","author":"Mahmoudi","year":"2021","journal-title":"Integr. 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