Igenomix Foundation, INCLIVA Instituto de Investigación Sanitaria, Valencia, Spain.
Igenomix Foundation, INCLIVA Instituto de Investigación Sanitaria, Valencia, Spain.
Am J Obstet Gynecol. 2022 Feb;226(2S):S886-S894. doi: 10.1016/j.ajog.2020.09.039. Epub 2020 Sep 29.
Preeclampsia is a major obstetrical complication with short- and long-term life-threatening consequences for both mother and child. Shallow cytotrophoblast invasion through the uterine decidua into the spiral arteries is implicated in the pathogenesis of preeclampsia, although the cause of deficient arterial invasion remains unknown. Research that is focused on the "soil"-the maternal decidua-highlights the importance of this poorly understood but influential uterine layer. Decidualization of endometrial cells regulates embryo invasion, which is essential for spiral artery remodeling and establishing the maternal-fetal interface. Exploration of the association between impaired decidualization and preeclampsia revealed suboptimal endometrial maturation and uterine natural killer cells present in the decidua before preeclampsia development. Furthermore, decidualization defects in the endometrium of women with severe preeclampsia, characterized by impaired cytotrophoblast invasion, were detected at the time of delivery and persisted 5 years after the affected pregnancy. Recently, a maternal deficiency of annexin A2 expression was found to influence aberrant decidualization and shallow cytotrophoblast invasion, suggesting that decidualization resistance, which is a defective endometrial cell differentiation during the menstrual cycle, could underlie shallow trophoblast invasion and the poor establishment of the maternal-fetal interface. Based on these findings, the transcriptional signature in the endometrium that promotes decidualization deficiency could be detected before (or after) conception. This would serve to identify women at risk of developing severe preeclampsia and aid the development of therapies focused on improving decidualization, perhaps also preventing severe preeclampsia. Here, we discuss decidualization deficiency as a contributor to the pathogenesis of pregnancy disorders with particular attention to severe preeclampsia. We also review current diagnostic strategies and discuss future directions in diagnostic methods based on decidualization.
子痫前期是一种主要的产科并发症，对母婴均有短期和长期的生命威胁。浅滋养细胞浸润穿透子宫蜕膜进入螺旋动脉被认为与子痫前期的发病机制有关，尽管动脉浸润不足的原因仍不清楚。专注于“土壤”-母体蜕膜-的研究强调了这个理解不足但有影响力的子宫层的重要性。子宫内膜细胞的蜕膜化调节胚胎浸润，这对于螺旋动脉重塑和建立母胎界面至关重要。探索蜕膜化受损与子痫前期之间的关联揭示了在子痫前期发展之前，子宫内膜成熟不足和蜕膜中存在的子宫自然杀伤细胞。此外，在重度子痫前期妇女的子宫内膜中检测到蜕膜化缺陷，其特征是滋养细胞浸润受损，这在分娩时和受影响妊娠 5 年后仍然存在。最近，发现母体 annexin A2 表达缺陷会影响异常的蜕膜化和浅滋养细胞浸润，这表明蜕膜化抵抗，即在月经周期中子宫内膜细胞分化缺陷，可能是浅滋养细胞浸润和母胎界面建立不良的基础。基于这些发现，可以在受孕前（或后）检测到促进蜕膜化缺陷的子宫内膜转录特征。这将有助于识别有发展为重度子痫前期风险的妇女，并有助于开发针对改善蜕膜化的治疗方法，也许还可以预防重度子痫前期。在这里，我们讨论蜕膜化缺陷作为妊娠疾病发病机制的一个因素，特别是重度子痫前期。我们还回顾了当前的诊断策略，并讨论了基于蜕膜化的未来诊断方法的方向。
