Persistent hypoxia induced autophagy leading to invasiveness of trophoblasts in placenta accreta
Persistent hypoxia induced autophagy leading to invasiveness of trophoblasts in placenta accreta
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DOI：
10.1080/14767058.2019.1635582
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发表时间：
2019-07-02
影响因子：
1.8
通讯作者：
Li, Huishu
中科院分区：
文献类型：
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作者：
Chen, Yunshan;Wang, Lele;Li, Huishu
背景：滋养细胞过度糜烂是侵入性胎盘的主要病理表现。与妊娠早期相似，侵入性胎盘的滋养层细胞在异常持续侵袭时也可能出现类似的缺氧状态，其中自噬也可能发生一些变化，导致植入性胎盘的侵袭能力发生变化。方法：根据植入标准收集10例植入性胎盘（植入性胎盘组）和10例非植入性胎盘（对照组）。采用免疫组化法检测缺氧诱导的自噬因子（HIF1α、Beclin 1、LC3B、P62）和侵袭相关标志物（E-cadherin、MMP-9）的表达。两组间评分等级比较采用Fisher精确检验，并采用Spearman检验进行相关分析。结果：HIF1α主要表达于滋养层细胞膜，植入胎盘组中度阳性50%（5/10）、强阳性50%（5/10），与对照组50%（5/10）或弱阳性30%（3/10）相比，差异有统计学意义（p < .05）。植入性胎盘组和对照组的 Beclin-1 表达阴性、弱阳性、中度阳性和强阳性率分别为 0、10、30 和 60%，而植入性胎盘组和对照组分别为 60、40、0 和 0%，差异有统计学意义 (p < .05)。 LC3B的表达在两组之间也有统计学显着性（0、10、20、70%与50、20、30、0%），并且P62的表达在两组之间也有统计学差异。 E-cadherin表达阳性率与Beclin-1、LC3B、P62表达呈明显负相关，MMP-9表达阳性率与自噬相关标志物呈正相关。结论：缺氧状态可能参与胎盘植入的发生，持续缺氧诱导的自噬紊乱可导致E-cadherin和MMP-9表达下调，从而导致胎盘滋养细胞更具侵袭性。
Background: Excessive trophoblasts erosivity is the main pathological manifestation in placenta accreta. Similar to early pregnancy, trophoblasts of placenta accreta might have a similar anoxic state in abnormal continuous invasion, in which autophagy may also have some changes causing invasive ability in accreta. Methods: Ten accreta placentas (placenta accreta group), as well as 10 non-accreta placentas (control group), were collected according to accreta criteria. The expression of hypoxia-induced autophage factors (HIF1 alpha, Beclin 1, LC3B, and P62) and invasion-related markers (E-cadherin and MMP-9) were detected using immunohistochemical method. Comparison in scores grade was made between the two groups by Fisher's exact test and Spearman's test was used for correlation analysis. Results: HIF1 alpha was mainly expressed in cytomembrane of trophoblasts, in which moderate positive 50% (5/10) and strong positive 50% (5/10) in placenta accreta group compared to 50% (5/10) or weak positive 30% (3/10) in control group, with a significant statistically difference (p < .05). The negative, weak positive, moderate positive, and strong positive rates of Beclin-1 expression were 0, 10, 30, and 60% versus 60, 40, 0, and 0% in placenta accreta group and control group, respectively, statistically different (p < .05). The expression of LC3B was also statistically significant (0, 10, 20, 70% versus 50, 20, 30, 0%) between two groups, and P62 expression was also statistically different between two groups. The positive rates of E-cadherin expression were obviously negatively correlated with Beclin-1, LC3B, and P62 expression, while positive rates of MMP-9 expression were positively correlated with autophagy-associated markers. Conclusions: Hypoxia state might be involved in the occurrence of placental accreta, and persistent hypoxia state induced autophage disorders could cause down-regulated E-cadherin and down-regulated MMP-9, thus leading to more invasiveness of placenta trophoblasts.