Persistent hypoxia induced autophagy leading to invasiveness of trophoblasts in placenta accreta

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 (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.

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.