Quan Duoduo, Cheng Yang, Zhou Xinhe, Xu Jiao, Shangguan Tingting, Tang Yibing, Zhao Zhiguang, Xu Qiang
Department of Pathology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Department of Pathology, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi 330000, China.
Curr Res Toxicol. 2025 Aug 14;9:100254. doi: 10.1016/j.crtox.2025.100254. eCollection 2025.
Linuron, a commonly used agricultural herbicide in certain regions, has raised concerns due to its endocrine toxicity in humans and wildlife. While its gonadal toxicity is established, its direct impact on prenatal adrenal development remains unexplored. Pregnant Sprague-Dawley rats received linuron doses (0, 25, 50, 100 mg/kg/day) by oral gavage from gestational days 12-21. Linuron reduced serum CORT at 50 and 100 mg/kg and ALDO at 100 mg/kg but did not affect ACTH levels. At 100 mg/kg, linuron decreased cell density in the adrenal zona fasciculata without changing its thickness. It also altered the expression of key genes and proteins involved in adrenal function at 50 and/or 100 mg/kg. Additionally, linuron reduced the expression of key antioxidant enzymes (SOD2, GPX1, CAT) at 100 mg/kg. Linuron altered adrenal kinase signaling, activating AMPK but suppressing AKT, with no effect on ERK1/2 pathways. These findings reveal, for the first time, that linuron disrupts male fetal adrenal development and function likely through impaired steroidogenesis, oxidative stress, and dysregulated AKT/AMPK signaling, highlighting its role as a developmental adrenal disruptor.
利谷隆是某些地区常用的一种除草剂，因其对人类和野生动物具有内分泌毒性而引发了人们的关注。虽然其性腺毒性已得到证实，但其对产前肾上腺发育的直接影响仍未得到探索。从妊娠第12天至21天，通过灌胃法给怀孕的斯普拉格-道利大鼠喂食不同剂量（0、25、50、100毫克/千克/天）的利谷隆。利谷隆在剂量为50和100毫克/千克时降低了血清皮质醇水平，在剂量为100毫克/千克时降低了血清醛固酮水平，但对促肾上腺皮质激素水平没有影响。在剂量为100毫克/千克时，利谷隆降低了肾上腺束状带的细胞密度，但未改变其厚度。在剂量为50和/或100毫克/千克时，它还改变了参与肾上腺功能的关键基因和蛋白质的表达。此外，利谷隆在剂量为100毫克/千克时降低了关键抗氧化酶（超氧化物歧化酶2、谷胱甘肽过氧化物酶1、过氧化氢酶）的表达。利谷隆改变了肾上腺激酶信号传导，激活了腺苷酸活化蛋白激酶但抑制了蛋白激酶B，对细胞外信号调节激酶1/2通路没有影响。这些发现首次揭示，利谷隆可能通过损害类固醇生成、氧化应激和失调的蛋白激酶B/腺苷酸活化蛋白激酶信号传导来破坏雄性胎儿肾上腺的发育和功能，突出了其作为一种发育性肾上腺干扰物的作用。
