Dong Xiujuan, Yang Long, Wang Hui
a Department of Gynecology and Obstetrics , Cangzhou Center Hospital , Cangzhou , Hebei Province , P.R. China and.
b Department of Gynecology and Obstetrics , The First People's Hospital of Shangqiu , Shangqiu , Henan Province , P.R. China.
Gynecol Endocrinol. 2017 Apr;33(4):274-278. doi: 10.1080/09513590.2016.1266476. Epub 2016 Dec 31.
The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.
成功妊娠的建立和维持主要依赖于滋养层细胞。它们的功能障碍与复发性自然流产（RSA）有关，RSA是妊娠的一种主要并发症。然而，滋养层细胞功能障碍的潜在机制仍不清楚。据报道，DNA损伤诱导的细胞凋亡在细胞死亡中起重要作用。在本研究中，我们通过调节滋养层细胞凋亡，在RSA进展过程中鉴定出一种新型微小RNA（miR-520）。微阵列分析显示，miR-520在RSA患者的绒毛中高表达。通过流式细胞术分析，我们观察到miR-520的表达与体外人滋养层细胞凋亡相关，同时聚（ADP-核糖）聚合酶-1（PARP1）表达降低。通过对临床样本的分析，我们观察到RSA绒毛中miR-520水平与PARP1水平呈负相关。此外, PARP1的过表达恢复了miR-520诱导的体外滋养层细胞凋亡。滋养层细胞中的染色体状态表明，miR-520通过促进DNA损伤诱导的细胞凋亡来调节RSA进展。这些结果表明，miR-520水平可能通过PARP1依赖的DNA损伤途径促进滋养层细胞凋亡，从而与RSA相关。
