Control of oviductal fluid flow by the G-protein coupled receptor Adgrd1 is essential for murine embryo transit.
Control of oviductal fluid flow by the G-protein coupled receptor Adgrd1 is essential for murine embryo transit.
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DOI：
10.1038/s41467-021-21512-w
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发表时间：
2021-02-23
影响因子：
16.6
通讯作者：
Wright GJ
中科院分区：
文献类型：
--
作者：
Bianchi E;Sun Y;Almansa-Ordonez A;Woods M;Goulding D;Martinez-Martin N;Wright GJ
胚胎运输功能障碍导致异位妊娠，影响美国和欧洲约2%的妊娠，是妊娠前三个月妊娠相关死亡的最常见原因。胚胎运输涉及一种类似阀门的输卵管闭锁现象，这种现象会暂时将卵母细胞阻滞在受精发生的壶腹峡部（AIJ），但所涉及的机制尚不清楚。在这里，我们表明，缺乏孤儿粘附G蛋白偶联受体Adgrd1的雌性小鼠是不育的，因为它们不能缓解AIJ抑制机制，不适当地将胚胎保留在输卵管内。Adgrd 1在输卵管上皮上表达，并且在Adgrd 1缺陷小鼠中输卵管液流量的排卵后衰减失调。使用大规模的细胞外蛋白质相互作用的屏幕，我们确定Plxdc 2作为激活配体的Adgrd 1展示在卵丘细胞。我们的研究结果表明，调节输卵管液流Adgrd1控制胚胎运输，我们提出了一个模型，其中在AIJ胚胎停滞是由于abovarial纤毛行动和adovarial输卵管液流的力量的平衡，在野生型输卵管，通过Adgrd1激活，使胚胎释放流体流量逐渐减弱。我们的研究结果为小鼠胚胎转运所涉及的分子机制提供了重要的见解。缺乏正确的胚胎运输可导致异位妊娠。在这里，作者表明，缺乏粘附G蛋白偶联受体Adgrd 1的雌性小鼠是不育的，这是由于输卵管液流失调导致胚胎被困在壶腹中。
Dysfunction of embryo transport causes ectopic pregnancy which affects approximately 2% of conceptions in the US and Europe, and is the most common cause of pregnancy-related death in the first trimester. Embryo transit involves a valve-like tubal-locking phenomenon that temporarily arrests oocytes at the ampullary-isthmic junction (AIJ) where fertilisation occurs, but the mechanisms involved are unknown. Here we show that female mice lacking the orphan adhesion G-protein coupled receptor Adgrd1 are sterile because they do not relieve the AIJ restraining mechanism, inappropriately retaining embryos within the oviduct. Adgrd1 is expressed on the oviductal epithelium and the post-ovulatory attenuation of tubal fluid flow is dysregulated in Adgrd1-deficient mice. Using a large-scale extracellular protein interaction screen, we identified Plxdc2 as an activating ligand for Adgrd1 displayed on cumulus cells. Our findings demonstrate that regulating oviductal fluid flow by Adgrd1 controls embryo transit and we present a model where embryo arrest at the AIJ is due to the balance of abovarial ciliary action and the force of adovarial tubal fluid flow, and in wild-type oviducts, fluid flow is gradually attenuated through Adgrd1 activation to enable embryo release. Our findings provide important insights into the molecular mechanisms involved in embryo transport in mice. Lack of correct embryo transport can cause ectopic pregnancy. Here, the authors show that female mice lacking the adhesion G-protein coupled receptor Adgrd1 are infertile, due to embryos being trapped in the ampulla as the result of dysregulated oviductal fluid flow.
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影响因子：
7
作者：
Bushell, K. Mark;Sollner, Christian;Wright, Gavin J.
通讯作者：
Wright, Gavin J.
影响因子：
11.4
作者：
Arac, Demet;Boucard, Antony A.;Bolliger, Marc F.;Nguyen, Jenna;Soltis, S. Michael;Suedhof, Thomas C.;Brunger, Axel T.
通讯作者：
Brunger, Axel T.
Semaphorin-7a是一种用于恶性疟原虫的红细胞受体。
影响因子：
6.7
作者：
Bartholdson SJ;Bustamante LY;Crosnier C;Johnson S;Lea S;Rayner JC;Wright GJ
通讯作者：
Wright GJ
影响因子：
2.5
作者：
Chen, Guangchun;Yang, Liquan;Begum, Shahinoor;Xu, Lei
通讯作者：
Xu, Lei
DOI：
10.1530/jrf.0.0060257
发表时间：
1963-01-01
期刊：
JOURNAL OF REPRODUCTION AND FERTILITY
影响因子：
--
作者：
BLACK, DL;DUBY, RT;RIESEN, J
通讯作者：
RIESEN, J