Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
J Matern Fetal Neonatal Med. 2021 Apr;34(8):1297-1303. doi: 10.1080/14767058.2019.1635582. Epub 2019 Jul 3.
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.
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 (HIF1α, 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.
HIF1α 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 ( < .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 ( < .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.
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.
过度的滋养细胞侵蚀性是胎盘植入的主要病理表现。类似于早期妊娠,胎盘植入的滋养细胞在异常的持续浸润中可能处于类似的缺氧状态,自噬也可能发生一些变化,导致植入物的浸润能力。
根据胎盘植入标准,收集 10 例胎盘植入胎盘(胎盘植入组)和 10 例非胎盘植入胎盘(对照组)。采用免疫组织化学法检测缺氧诱导的自噬因子(HIF1α、Beclin 1、LC3B 和 P62)和侵袭相关标志物(E-cadherin 和 MMP-9)的表达。Fisher 确切检验比较两组间的评分等级,Spearman 检验用于相关性分析。
HIF1α主要表达于滋养细胞的细胞膜上,胎盘植入组中中度阳性 50%(5/10)和强阳性 50%(5/10),对照组中 50%(5/10)或弱阳性 30%(3/10),差异有统计学意义(<0.05)。Beclin-1 表达的阴性、弱阳性、中度阳性和强阳性率分别为 0、10、30 和 60%,而胎盘植入组和对照组分别为 60、40、0 和 0%,差异有统计学意义(<0.05)。LC3B 的表达也有统计学意义(0、10、20、70%,对照组为 50、20、30、0%),P62 的表达在两组间也有统计学差异。E-cadherin 表达的阳性率与 Beclin-1、LC3B 和 P62 的表达呈明显负相关,而 MMP-9 表达的阳性率与自噬相关标志物呈正相关。
缺氧状态可能参与胎盘植入的发生,持续的缺氧状态诱导自噬紊乱可能导致 E-cadherin 下调和 MMP-9 下调,从而导致胎盘滋养细胞的侵袭性增加。