Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, China.
Department of Bioinformatics, School of Basic Medicine, Chongqing Medical University, Chongqing, China.
Mol Hum Reprod. 2022 Apr 29;28(5). doi: 10.1093/molehr/gaac014.
Human cytotrophoblast (CTB) differentiation into syncytiotrophoblast (STB) is essential for placental formation and function. Understanding the molecular mechanisms involved in trophoblast differentiation is necessary as it would help in the development of novel therapeutic agents to treat placentation-mediated pregnancy complications. In this study, we found a common upregulated gene, ADAM-like Decysin-1 (ADAMDEC1), from five published microarray and RNA-sequencing datasets. Interference to ADAMDEC1 impaired forskolin-induced BeWo cells differentiation, while ADAMDEC1 overexpression promoted BeWo cells and 3D JEG-3 spheroids differentiation. Interestingly, ADAMDEC1 may inhibit Thrombospondin 1 rather than E-cadherin to trigger the activation of the cAMP signal pathway during CTB differentiation into STB. More importantly, a decreasing in ADAMDEC1 might be involved in the development of preeclampsia. Therefore, ADAMDEC1 is expected to become a new target for prediction of and intervention in placenta-derived pregnancy diseases.
人类细胞滋养层（CTB）向合体滋养层（STB）的分化对于胎盘的形成和功能至关重要。了解参与滋养层分化的分子机制对于开发新型治疗药物以治疗胎盘介导的妊娠并发症非常必要。在这项研究中，我们从五个已发表的微阵列和 RNA 测序数据集中找到了一个共同上调的基因，即 ADAM 样解整合素 1（ADAMDEC1）。干扰 ADAMDEC1 会损害 forskolin 诱导的 BeWo 细胞分化，而 ADAMDEC1 过表达则促进 BeWo 细胞和 3D JEG-3 球体的分化。有趣的是，ADAMDEC1 可能通过抑制血小板反应蛋白 1（TSP1）而不是 E-钙黏蛋白来触发 CTB 向 STB 分化过程中 cAMP 信号通路的激活。更重要的是，ADAMDEC1 的减少可能与子痫前期的发生有关。因此，ADAMDEC1 有望成为预测和干预胎盘源性妊娠疾病的新靶点。
