Loss of MIG-6 results in endometrial progesterone resistance via ERBB2.
Loss of MIG-6 results in endometrial progesterone resistance via ERBB2.
复制标题
DOI：
10.1038/s41467-022-28608-x
复制
发表时间：
2022-03-01
影响因子：
16.6
通讯作者：
Jeong JW
中科院分区：
文献类型：
--
作者：
Yoo JY;Kim TH;Shin JH;Marquardt RM;Müller U;Fazleabas AT;Young SL;Lessey BA;Yoon HG;Jeong JW
女性生育力低下与子宫内膜异位症高度相关。子宫内膜孕酮抵抗被认为是子宫内膜疾病发展的关键因素。我们报道了子宫内膜异位症不孕妇女和非人灵长类动物子宫内膜异位症模型中，TGF-β 6表达下调。我们在子宫特异性Mig-6敲除小鼠（Pgrcre/+Mig-6 f/f; Mig-6d/d）的子宫内膜中发现ERBB 2过表达。为了研究ERBB 2靶向对子宫内膜孕酮抵抗、生育力和子宫内膜异位症的影响，我们在Mig-6d/d小鼠（Mig-6d/dErbb 2d/d小鼠）中引入Erbb 2消融。Erbb 2的额外敲除挽救了Mig-6d/d小鼠中观察到的所有表型。转录组学分析显示，在Mig-6d/d小鼠中差异表达的基因在Mig-6d/dErbb 2d/d小鼠中恢复到其正常表达。总之，我们的研究结果表明，ERBB 2在子宫内膜中的过度表达与ER-6缺乏导致子宫内膜孕酮抵抗和子宫内膜异位症相关不孕症的非接受性子宫内膜，ERBB 2靶向逆转这些影响。女性生育力低下与子宫内膜异位症高度相关。在这里，作者表明，在不孕妇女和患有子宫内膜异位症的非人灵长类动物的子宫内膜中，孕酮诱导的Erbb-6减少，并且在小鼠模型中发现Erbb 2是Mig-6损失诱导的子宫内膜异位症相关不孕症的关键介质。
Female subfertility is highly associated with endometriosis. Endometrial progesterone resistance is suggested as a crucial element in the development of endometrial diseases. We report that MIG-6 is downregulated in the endometrium of infertile women with endometriosis and in a non-human primate model of endometriosis. We find ERBB2 overexpression in the endometrium of uterine-specific Mig-6 knockout mice (Pgrcre/+Mig-6f/f; Mig-6d/d). To investigate the effect of ERBB2 targeting on endometrial progesterone resistance, fertility, and endometriosis, we introduce Erbb2 ablation in Mig-6d/d mice (Mig-6d/dErbb2d/d mice). The additional knockout of Erbb2 rescues all phenotypes seen in Mig-6d/d mice. Transcriptomic analysis shows that genes differentially expressed in Mig-6d/d mice revert to their normal expression in Mig-6d/dErbb2d/d mice. Together, our results demonstrate that ERBB2 overexpression in endometrium with MIG-6 deficiency causes endometrial progesterone resistance and a nonreceptive endometrium in endometriosis-related infertility, and ERBB2 targeting reverses these effects. Female subfertility is highly associated with endometriosis. Here the authors show that progesterone-induced MIG-6 is reduced in endometrium of infertile women and non-human primates with endometriosis, and in a mouse model find that Erbb2 is the key mediator of Mig-6 loss induced endometriosis-related infertility.
登录
查看更多内容
影响因子：
82.9
作者：
Cha J;Sun X;Dey SK
通讯作者：
Dey SK
影响因子：
5.3
作者：
Fiorentino, L;Pertica, C;Segatto, O
通讯作者：
Segatto, O
DOI：
10.1111/j.1749-6632.2002.tb02791.x
发表时间：
2002-01-01
期刊：
ENDOMETRIOSIS: EMERGING RESEARCH AND INTERVENTION STRATEGIES
影响因子：
--
作者：
Fazleabas, AT;Brudney, A;Bulun, S
通讯作者：
Bulun, S
DOI：
10.1016/s0889-8545(05)70302-8
发表时间：
1997-06-01
影响因子：
3.2
作者：
Eskenazi, B;Warner, ML
通讯作者：
Warner, ML
DOI：
10.1111/aji.12473
发表时间：
2016-03
期刊：
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子：
--
作者：
Bhurke AS;Bagchi IC;Bagchi MK
通讯作者：
Bagchi MK