Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University East Lansing, MI 48824, USA.
Institute for Quantitative Health Science and Engineering, Michigan State University East Lansing, MI 48824, USA.
Development. 2020 Dec 21;147(24):dev193490. doi: 10.1242/dev.193490.
How a mammalian embryo determines and arrives at its attachment site has been studied for decades, but our understanding of this process is far from complete. Using confocal imaging and image analysis, we evaluate embryo location along the longitudinal oviductal-cervical axis of murine uteri. Our analysis reveals three distinct pre-implantation phases: embryo entry, unidirectional movement of embryo clusters and bidirectional scattering and spacing of embryos. We show that unidirectional clustered movement is facilitated by a mechanical stimulus of the embryo and is regulated by adrenergic uterine smooth muscle contractions. Embryo scattering, on the other hand, depends on embryo-uterine communication reliant on the LPAR3 signaling pathway and is independent of adrenergic muscle contractions. Finally, we demonstrate that uterine implantation sites in mice are neither random nor predetermined but are guided by the number of embryos entering the uterine lumen. These studies have implications for understanding how embryo-uterine communication is key to determining an optimal implantation site necessary for the success of a pregnancy.
几十年来，人们一直在研究哺乳动物胚胎如何确定并到达其附着点，但我们对这一过程的理解还远不完整。我们使用共聚焦成像和图像分析来评估胚胎在鼠子宫的输卵管-宫颈纵轴上的位置。我们的分析揭示了三个不同的着床前阶段：胚胎进入、胚胎簇的单向运动以及胚胎的双向散射和间隔。我们表明，单向聚集运动是由胚胎的机械刺激促进的，并受到肾上腺素能子宫平滑肌收缩的调节。另一方面，胚胎散射依赖于依赖 LPAR3 信号通路的胚胎-子宫通讯，并且独立于肾上腺素能肌肉收缩。最后，我们证明小鼠的子宫着床部位不是随机的也不是预先确定的，而是由进入子宫腔的胚胎数量决定的。这些研究对于理解胚胎-子宫通讯如何是确定最佳着床部位的关键，而着床部位对于妊娠的成功是必要的。
