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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Endometrial calbindins are critical for embryo implantation: Evidence from in vivo use of morpholino antisense oligonucleotides.
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Endometrial calbindins are critical for embryo implantation: Evidence from in vivo use of morpholino antisense oligonucleotides.

机译：子宫内膜calbindins对于胚胎植入至关重要：体内使用吗啉代反义寡核苷酸的证据。

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摘要

The endometrium is receptive to embryo implantation only for a short period in each reproductive cycle: development of receptivity requires alterations in endometrial gene expression. Calbindin (CaBP)-d9k and CaBP-d28k are related proteins containing EF hand motifs that have a high affinity for Ca(2+). We previously demonstrated that endometrial expression of CaBP-d9k mRNA is highly regulated during implantation in the mouse. This project aimed to determine the temporal and spatial expression of both CaBP proteins during early pregnancy and to establish whether they are necessary for blastocyst implantation. CaBP-d28k protein, like CaBP-d9k, was up-regulated in the endometrial epithelium just before implantation but disappeared at implantation sites after attachment. By the judicious intrauterine injection of morpholino oligonucleotides (MO) against CaBP-d9k into WT and CaBP-d28k null mice just before implantation, we selectively eliminated one or both CaBPs from the uterine epithelium. Implantation was blocked only when both CaBP-d9k and CaBP-d28k were absent: treated WT mice and untreated CaBP-d28k null mice were fertile. Furthermore, the effect on implantation was highly dependent on the timing of injection of MO. This report examining the function of implantation-related genes in the uterus using MO demonstrates that this technique is a highly effective means to specifically target uterine proteins in vivo. This study provides evidence for an absolute requirement for CaBPs during the early phase of embryo implantation, and thus that regulation of Ca(2+) availability in the uterine environment of the implanting embryo is critical for successful implantation.
机译：在每个生殖周期中，子宫内膜仅在短时间内接受胚胎植入：接受性的发展需要子宫内膜基因表达的改变。钙结合蛋白（CaBP）-d9k和CaBP-d28k是包含EF手基序对Ca（2+）具有高亲和力的相关蛋白。我们以前证明，CaBP-d9k mRNA的子宫内膜表达在小鼠体内植入过程中受到高度调节。该项目旨在确定妊娠早期两种CaBP蛋白的时空表达，并确定它们是否为胚泡植入所必需。 CaBP-d28k蛋白与CaBP-d9k一样，在植入前即在子宫内膜上皮中被上调，但在附着后在植入部位消失。通过在植入前向WT和CaBP-d28k null小鼠明智地宫内注射针对CaBP-d9k的吗啉代寡核苷酸（MO），我们选择性地从子宫上皮中消除了一个或两个CaBP。仅当CaBP-d9k和CaBP-d28k均不存在时才阻止植入：处理过的WT小鼠和未处理过的CaBP-d28k无效小鼠可育。此外，对植入的影响高度依赖于MO注射的时间。这份使用MO检查子宫内植入相关基因功能的报告证明，该技术是在体内特异性靶向子宫蛋白的高效方法。这项研究为胚胎植入早期阶段对CaBP的绝对需求提供了证据，因此，对胚胎植入子宫环境中Ca（2+）可用性的调节对于成功植入至关重要。

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