The Possible Role of Hypoxia-induced Autophagy and Matrix Metalloproteinase-9 in the Pathogenesis of Morbidly Adherent Placenta.

Cesarean section (CS) rate has been rising rapidly in the recent years.One of the complications of repeated CS is placenta previa, an implantation of placenta on or near internal os.

Morbidly adherent placenta (MAP), known also as placenta accreta spectrum, has histopathologic and clinical types. The placenta becomes abnormally adherent to the uterine wall, fails to separate leading to massive blood loss and possible hysterectomy. The risk of MAP in patient with placenta previa increases with repeated CS.

Theories for development of MAP include abnormal trophoblastic invasion of myometrium, abnormal decidualization, neovascularization and reduction of apoptosis of trophobalsts.

In early pregnancy: the trophoblasts invade spiral arteries and reduce blood flow to the placenta 00leading to hypoxia. Hypoxia inducible factor 1 alpha (HIF-1α), a protein involved in cellular adaptation to hypoxia, increases throughout pregnancy and contributes in the invasion of trophoblasts. Excessive invasion in MAP might prolong the hypoxia, increasing the expression of HIF1α.

Autophagy is a process for managing and removing the damaged organelles and cellular proteins in hypoxia. It supports the trophoblasts. Hypoxia induced autophagy markers such as LC3B might be enhanced by MAP.