Erythropoietin-producing hepatocellular A7 triggering ovulation indicates a potential beneficial role for polycystic ovary syndrome.
Erythropoietin-producing hepatocellular A7 triggering ovulation indicates a potential beneficial role for polycystic ovary syndrome.
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产生促红细胞生成素的肝细胞 A7 触发排卵表明对多囊卵巢综合征具有潜在的有益作用。
DOI：
10.1016/j.ebiom.2018.09.046
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发表时间：
2018-10
期刊：
影响因子：
11.1
通讯作者：
Du Y
中科院分区：
文献类型：
--
作者：
Li S;Zhai J;Liu J;Di F;Sun Y;Li W;Chen ZJ;Du Y
多囊卵巢综合征（PCOS）的排卵功能障碍机制尚不完全清楚。而EPHA7及EPHA7调控的通路因子在无排卵的发病机制中的作用仍有待阐明。我们利用PCOS和非PCOS患者的人颗粒细胞（hGCs）检测EPHA7等靶基因的表达。我们在KGN细胞中进行了体外实验以验证其分子机制。此外，我们使用EPHA7 shRNA慢病毒和重组EPHA7- fc蛋白注射剂进行了体内功能丧失和功能获得的研究，以确定EPHA7对排卵的影响。EPHA7是erk1 /2介导的C/EBPβ表达的关键阳性上游因子。该蛋白依次诱导KLF4和ADAMTS1的表达。PCOS患者hgc中EPHA7丰度的降低与其下游因子丰度的降低呈正相关。此外，EPHA7 shRNA慢病毒在大鼠卵巢中1周的功能导致卵母细胞数量减少，3周的功能慢病毒导致大鼠卵巢月经紊乱和形态学多囊变化。更重要的是，我们发现EPHA7可触发大鼠排卵，改善PCOS大鼠DHEA诱导的多囊卵巢变化。我们的研究结果表明EPHA7在PCOS中的新作用，提示EPHA7是开发促排卵创新药物的有效靶点。国家重点研发计划、国家自然科学基金、上海市教委——高峰临床医学、上海市科学技术委员会。
The ovulatory dysfunction mechanisms underlying polycystic ovary syndrome (PCOS) are not completely understood. And the roles of EPHA7 and EPHA7-regulated pathway factors in the pathogenesis of anovulation remain to be elucidated. We used human granulosa cells (hGCs) of PCOS and non-PCOS patients to measure EPHA7 and other target gene expressions. We performed in vitro experiments in KGN cells to verify the molecular mechanisms. Additionally, we conducted in vivo loss- and gain-of-function studies using EPHA7 shRNA lentivirus and recombinant EPHA7-Fc protein injection to identify the ovulation effects of EPHA7. EPHA7 functions as a critically positive upstream factor for the expression of ERK1/2-mediated C/EBPβ. This protein, in turn, induced the expression of KLF4 and then ADAMTS1. Moreover, decreased abundance of EPHA7 was positively correlated with that of its downstream factors in hGCs of PCOS patients. Additionally, a 1-week functional EPHA7 shRNA lentivirus in rat ovaries contributed to decreased numbers of retrieved oocytes, and a 3-week functional lentivirus led to menstrual disorders and morphological polycystic changes in rat ovaries. More importantly, we found that EPHA7 triggered ovulation in rats, and it improved polycystic ovarian changes induced by DHEA in PCOS rats. Our findings demonstrate a new role of EPHA7 in PCOS, suggesting that EPHA7 is an effective target for the development of innovative medicines to induce ovulation. National Key Research and Development Program of China, National Natural Science Foundation, Shanghai Municipal Education Commission--Gaofeng Clinical Medicine, and Shanghai Commission of Science and Technology.
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DOI：
10.1126/science.1171396
发表时间：
2009-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fan HY;Liu Z;Shimada M;Sterneck E;Johnson PF;Hedrick SM;Richards JS
通讯作者：
Richards JS
影响因子：
10.5
作者：
Duggavathi, Rajesha;Volle, David H.;Schoonjans, Kristina
通讯作者：
Schoonjans, Kristina
影响因子：
4.6
作者：
Galvão AM;Ferreira-Dias G;Skarzynski DJ
通讯作者：
Skarzynski DJ
DOI：
10.1016/j.bbrc.2012.02.164
发表时间：
2012-04-06
影响因子：
3.1
作者：
Chen, Huatao;Chu, Guiyan;Hattori, Masa-aki
通讯作者：
Hattori, Masa-aki
影响因子：
25
作者：
Himanen, JP;Chumley, MJ;Nikolov, DB
通讯作者：
Nikolov, DB