MiR-7 Mediates the Zearalenone Signaling Pathway Regulating FSH Synthesis and Secretion by Targeting FOS in Female Pigs
MiR-7 Mediates the Zearalenone Signaling Pathway Regulating FSH Synthesis and Secretion by Targeting FOS in Female Pigs
复制标题
MiR-7 通过靶向 FOS 介导母猪玉米赤霉烯酮信号通路调节 FSH 合成和分泌
DOI：
10.1210/en.2018-00097
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发表时间：
2018-08-01
期刊：
影响因子：
4.8
通讯作者：
Cui, Sheng
中科院分区：
文献类型：
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作者：
He, Jing;Zhang, Jinglin;Cui, Sheng
玉米赤霉烯酮（ZEA）是一种环境内分泌干扰物（EED），可引起健康问题。据报道，miRNAs影响垂体激素的合成和分泌。然而，ZEA和miRNA之间的相互作用及其相关机制尚不清楚。本研究的目的是确定miR-7是否以及如何通过与猪垂体中的ZEA相互作用影响动物生殖，猪垂体对ZEA敏感，并已被用作医学研究的重要动物模型。采用实时荧光定量PCR、原位杂交和免疫组化方法检测miRNA的表达。ZEA、miR-7及其相互作用在垂体中的作用通过使用卵巢切除的猪模型、检测miR-7模拟物和抑制剂、放射免疫测定、荧光素酶报告基因测定和蛋白质印迹来鉴定。ZEA的体内剂量为7.5 mg/kg体重，体外剂量为1 μM。我们的研究结果表明miR-7可以调节促性腺激素的合成和分泌。此外，我们发现ZEA通过增强miR-7的表达，从而抑制FSH的合成和分泌，从而导致生殖缺陷。体内外实验表明，ZEA的作用依赖于G蛋白偶联雌激素受体1，miR-7通过介导ZEA信号通路和靶向Finkel-Biskis-Jinkins鼠骨肉瘤病毒癌基因同源物（FOS）基因发挥作用。这些结果表明，miRNAs是通过介导垂体EED信号调节垂体促性腺激素的关键内在因子，miRNAs和EED的作用在医疗实践和动物生产中应得到重视。
Zearalenone (ZEA) acts as an environmental endocrine disruptor (EED) to cause health detriments. miRNAs were reported to influence the synthesis and secretion of pituitary hormones. However, the interactions between ZEA and miRNAs and related mechanisms remain unclear. The aims of this study were to determine whether and how miR-7 affects animal reproduction by its interactions with ZEA in the pig pituitary, which is sensitive to ZEA and has been used as an important animal model in medical research. Expressions of miRNA were detected by real-time PCR, in situ hybridization, and immunohistochemistry. The effects of ZEA, miR-7, and their interactions in the pituitary gland were identified by using an ovariectomized pig model, transfecting miR-7 mimics and inhibitor, radioimmunoassay, luciferase reporter assay, and Western blotting. The ZEA dosage was 7.5 mg/kg body weight in vivo and 1 μM in vitro. Our results demonstrate miR-7 acts to regulate gonadotropin synthesis and secretion. Furthermore, we found that ZEA leads to reproductive defects by enhancing miR-7 expression, which subsequently inhibits FSH synthesis and secretion. In vitro and in vivo experiments revealed that the effects of ZEA rely on G protein-coupled estrogen receptor 1, and miR-7 functions by mediating ZEA signaling pathway and targeting the Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (FOS) gene. These findings show that miRNAs are key intrinsic factors regulating pituitary gonadotropins by mediating EED signaling in pituitary glands, and the actions of miRNAs and EEDs should be seriously considered in related studies about medical practice and animal production.