{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T13:21:49Z","timestamp":1776864109228,"version":"3.51.2"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Programs of China","award":["2023YFD1301005"],"award-info":[{"award-number":["2023YFD1301005"]}]},{"name":"National Key Research and Development Programs of China","award":["2024TZXD027"],"award-info":[{"award-number":["2024TZXD027"]}]},{"name":"National Key Research and Development Programs of China","award":["2023TZXD041"],"award-info":[{"award-number":["2023TZXD041"]}]},{"name":"Shandong Province Pig Industry Technology System","award":["SDAIT-08-04"],"award-info":[{"award-number":["SDAIT-08-04"]}]},{"name":"Shandong Province Pig Industry Technology System","award":["SDAIT-08-05"],"award-info":[{"award-number":["SDAIT-08-05"]}]},{"name":"Taian Daizong Talent Program for Innovation and Entrepreneurship","award":["DZRC202311"],"award-info":[{"award-number":["DZRC202311"]}]},{"name":"Shandong Province Agricultural Major Technology Collaborative Promotion Plan","award":["SDNYXTTG-2025-43"],"award-info":[{"award-number":["SDNYXTTG-2025-43"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Zearalenone (ZEA) is a potent estrogenic mycotoxin known to disrupt reproductive functions, but its precise central neuroendocrine mechanisms remain unclear. This study investigated the effects of ZEA on the hypothalamic-pituitary Kiss1\/GPR54 signaling pathway in weaned gilts. A total of 32 gilts were randomly assigned to four dietary treatments contained with 0, 0.15, 1.5, or 3.0 mg\/kg ZEA for a 32-day feeding trial. Histopathology, immunohistochemistry, and mRNA\/protein expression analyses of GPR30, Kiss1, GPR54, GnRH, and GnRHR in the hypothalamus and pituitary gland were conducted. ZEA exposure induced significant histological damage in both tissues. In the hypothalamus, Kiss1, GPR54, GnRH, and GnRHR exhibited a non-linear response, increasing at moderate doses and decreasing at 3.0 mg\/kg ZEA, whereas GPR30 expression was continuously upregulated. In the pituitary gland, GnRHR showed a similar non-linear pattern. Furthermore, high-dose ZEA down-regulated pituitary Kiss1 and GPR54 while up-regulating GnRH and GPR30 expressions. In conclusion, ZEA induces reproductive neuroendocrine toxicity through a complex, dose-dependent modulation of the Kiss1\/GPR54 signaling axis. The persistent upregulation of GPR30 suggests it acts as a crucial mediator in disrupting this endocrine feedback loop within the hypothalamus and pituitary gland.<\/jats:p>","DOI":"10.3390\/toxins18050195","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T12:00:32Z","timestamp":1776859232000},"page":"195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Zearalenone on the Kiss1\/GPR54 System and Related Genes Expression in the Hypothalamus and Pituitary Gland of Weaned Gilts"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6482-8533","authenticated-orcid":false,"given":"Zixue","family":"Yuan","sequence":"first","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Luan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Kong","sequence":"additional","affiliation":[{"name":"Shandong Provincial Animal Husbandry General Station, Jinan 250109, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiren","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4943-0322","authenticated-orcid":false,"given":"Shuzhen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Efficient Utilization of Non-Grain Feed Resources (Co-Construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Shandong Agricultural University, Tai\u2019an 271017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s40104-021-00603-0","article-title":"Occurrence of aflatoxin B1, deoxynivalenol and zearalenone in feeds in China during 2018\u20132020","volume":"12","author":"Zhao","year":"2021","journal-title":"J. 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