{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:04:15Z","timestamp":1789621455932,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"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":["32573315"],"award-info":[{"award-number":["32573315"]}],"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":["32372965"],"award-info":[{"award-number":["32372965"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32573315"],"award-info":[{"award-number":["32573315"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32372965"],"award-info":[{"award-number":["32372965"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Exogenous gonadotropin-based estrus synchronization is widely used in livestock reproduction. However, this hormonal treatment has been associated with adverse reproductive outcomes, suggesting that it may alter the uterine environment and endometrial receptivity, although the underlying molecular mechanism remains poorly understood. Here, we investigated the endometrial responses to gonadotropin-induced estrus synchronization using both in vivo and in vitro models. We found that gonadotropin treatment caused structural and inflammatory changes in the endometrium of both pigs and mice, accompanied by elevated circulating estradiol (E2) levels and enhanced NLRP3 inflammasome-related signaling. In mice, gonadotropin treatment also altered the expression of MUC1, Hand2, and HoxA11, indicating disruption of molecular features associated with endometrial receptivity. In porcine endometrial epithelial cells, supraphysiological E2 exposure induced mitochondrial oxidative stress, characterized by increased mitochondrial reactive oxygen species production, loss of mitochondrial membrane potential, increased cellular mtDNA abundance, and oxidative DNA damage. E2 treatment further promoted NLRP3 inflammasome-associated signaling and ASC speck formation, whereas antioxidant N-acetyl-L-cysteine treatment attenuated ASC speck formation. Collectively, these findings support a link between high E2 exposure, mitochondrial oxidative stress, and enhanced NLRP3 inflammasome signaling in endometrial epithelial cells. Our results suggest that an E2\u2013mitochondrial oxidative stress\u2013NLRP3 axis may contribute to gonadotropin-associated endometrial dysfunction and provide a basis for further investigation of antioxidant and inflammasome-targeted strategies in livestock reproduction.<\/jats:p>","DOI":"10.3390\/antiox15091170","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:57:34Z","timestamp":1789473454000},"page":"1170","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Supraphysiological Estrogen Induces Endometrial Impairments via Mitochondrial ROS-Driven NLRP3 Inflammasome Activation"],"prefix":"10.3390","volume":"15","author":[{"given":"Yiran","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"}]},{"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Jiangxue","family":"Cai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Chenxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Jianguo","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8019-8480","authenticated-orcid":false,"given":"Bin","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing 210095, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s40104-024-01109-1","article-title":"Dietary Supplementation with N-Acetyl-L-Cysteine Ameliorates Hyperactivated ERK Signaling in the Endometrium That Is Linked to Poor Pregnancy Outcomes Following Ovarian Stimulation in Pigs","volume":"15","author":"Cheng","year":"2024","journal-title":"J. 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