{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:43:18Z","timestamp":1776058998872,"version":"3.50.1"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS), is a common endocrine disorder associated with chronic inflammation, affecting reproductive health in women. Chronic inflammation is a core driver of PCOS, highlighting the urgent need for interventions that target the underlying inflammatory pathogenesis of PCOS. Sheep placenta extract (SPE), as a traditional medicinal substance with multiple biological effects, including anti-inflammation, has been suggested to offer potential therapeutic benefits in managing chronic inflammation associated with PCOS. Treg dysfunction has emerged as a critical role in many diseases related to chronic inflammation. However, the role of SPE and its anti-inflammation mechanisms related to Treg in PCOS remains underexplored. The gut microbiota (GM) exerts a pivotal role in the pathogenesis and progression of numerous inflammatory disorders. Accordingly, further research is needed to investigate how SPE influences the gut microbial composition. The PCOS model was induced in rats using letrozole, and the animals were then administered SPE. Inflammatory cytokine, sex steroid hormone levels, markers of metabolic, transcriptomics, and 16S rRNA sequencing were assessed. SPE significantly alleviated abnormal ovarian histopathology in PCOS rats. SPE treatment suppressed inflammation by upregulating regulatory T cells (Tregs), with their anti-inflammatory effect mediated through the ER\u03b2-TGF\u03b21-Smad3 signaling pathway. SPE may ameliorate pathological damage in ovarian tissue of PCOS rats by exerting anti-inflammatory effects through the estrogen receptor \u03b2 (ER\u03b2)\/regulatory T cell (Treg) axis mediated by TGF-\u03b21\/Smad3 signaling, alonged with rectifying gut dysbiosis. Further study will focus on the proteomics strategy for identifying SPE, larger-scale validation of samples and comparisons with metformin or GLP-1 receptor agonists.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1777841","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T04:47:39Z","timestamp":1776055659000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sheep placental extract ameliorates polycystic ovary syndrome in rats by regulating ER\u03b2-mediated Treg cells via the TGF-\u03b21\/Smad3 signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Cunlin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathogenic Biology and Medical Immunology, Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijia","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Biology and Medical Immunology, Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinmeng","family":"Xing","sequence":"additional","affiliation":[{"name":"College of Labratory Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Tang","sequence":"additional","affiliation":[{"name":"Yinchuan Yibaisheng Bio-engineering Co., Ltd","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liru","family":"Jia","sequence":"additional","affiliation":[{"name":"Yinchuan Yibaisheng Bio-engineering Co., Ltd","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingrong","family":"He","sequence":"additional","affiliation":[{"name":"Yinchuan Yibaisheng Bio-engineering Co., Ltd","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junbai","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Biology and Medical Immunology, Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Biology and Medical Immunology, Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Biology and Medical Immunology, Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]},{"name":"College of Laboratory Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathogenic Biology and Medical Immunology, Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2025.1514250","article-title":"Global burden of polycystic ovary syndrome among women of childbearing age, 1990\u20132021: A systematic analysis using the global burden of disease study 2021","volume":"13","author":"Meng","year":"2025","journal-title":"Front Public Health"},{"key":"B2","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jsbmb.2009.12.010","article-title":"Insulin and hyperandrogenism in women with polycystic ovary syndrome","volume":"122","author":"Baptiste","year":"2010","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2007.07.009","article-title":"Polycystic ovary syndrome","volume":"22","author":"Homburg","year":"2008","journal-title":"Best Pract Res Clin Obstet. 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