The Hudson Institute of Medical Research, Clayton, Australia.
Department of Medicine, Monash University, Clayton, Australia.
Sci Rep. 2019 Oct 29;9(1):15495. doi: 10.1038/s41598-019-51751-3.
The yin and yang of female fertility is a complicated issue; large numbers of women/couples desire fertility and seek assisted reproduction intervention to achieve conception, while others seek to prevent pregnancy. Understanding specific molecules which control endometrial-embryo interactions is essential for both facilitating and preventing pregnancy. SOX17 has recently emerged as an important transcription factor involved in endometrial receptivity and embryo implantation. However, studies to date have examined mouse models of pregnancy which do not necessarily translate to the human. Demonstration of a role for 'implantation factors' in a human system is critical to provide a rationale for in depth clinical investigation and targeting of such factors. We demonstrate that SOX17is present within the receptive human endometrium and is up-regulated within human endometrial epithelial cells by combined estrogen & progesterone, the hormonal milieu during the receptive window. SOX17 localizes to the point of adhesive contact between human endometrial epithelial cells and a human 'embryo mimic' model (trophectodermal spheroid). Targeting SOX17 in endometrial epithelial cells using CRISPR/Cas9 knockdown or a SOX-F family inhibitor, MCC177, significantly inhibited adhesion of an trophectodermal spheroids to the epithelial cells thereby preventing 'implantation'. These data confirm the important role of endometrial SOX17 in human endometrial receptivity and embryo implantation.
女性生育力的阴阳是一个复杂的问题；大量的女性/夫妇渴望生育并寻求辅助生殖干预来实现受孕，而另一些则寻求避孕。了解控制子宫内膜-胚胎相互作用的特定分子对于促进和预防妊娠都是至关重要的。SOX17 最近作为一个涉及子宫内膜容受性和胚胎着床的重要转录因子而出现。然而，迄今为止的研究检查了怀孕的小鼠模型，这些模型不一定能转化为人类。在人类系统中证明“着床因子”的作用对于提供深入的临床研究和针对这些因子的靶向治疗的合理性至关重要。我们证明 SOX17 存在于接受状态的人类子宫内膜中，并在雌激素和孕激素联合作用下，在人类子宫内膜上皮细胞中被上调，这是接受窗口期间的激素环境。SOX17 定位于人类子宫内膜上皮细胞与人类“胚胎模拟物”模型（滋养层球体）之间的粘附接触点。使用 CRISPR/Cas9 敲低或 SOX-F 家族抑制剂 MCC177 靶向子宫内膜上皮细胞中的 SOX17，显著抑制滋养层球体与上皮细胞的粘附，从而阻止“着床”。这些数据证实了子宫内膜 SOX17 在人类子宫内膜容受性和胚胎着床中的重要作用。
