Decidual Vasculopathy and Spiral Artery Remodeling Revisited III: Hypoxia and Re-oxygenation Sequence with Vascular Regeneration

Aim: Spiral artery remodeling at early pregnancy is characterized by two distinct mechanisms with two morphologic features, namely, trophoblastic-dependent vascular invasion with “plugging”, and trophoblastic-independent mural muscular hypertrophy/hyperplasia, both of which lead to the blocking or narrowing of the arterial lumen with the consequence of reduced maternal blood flow to the developing embryo. Methods: Review of historic literature in light of the new discovery of CD56 (NCAM) expression on endovascular trophoblasts at late gestation, in relation to placental lateral growth with vascular regeneration. Results: Reduced maternal blood flow to the embryo results in a hypoxic condition critical for trophectoderm differentiation and proliferation. Hypoxia is also important for the development of hemangioblasts of vasculogenesis, and hematopoiesis of the placental villi. Up to 13 weeks, both uteroplacental and fetoplacental circulations are established and hypoxic condition relieved for normal fetal/placenta development by ultrasonography. The persistence of trophoblastic plugging and/or mural muscular hypertrophy/hyperplasia leads to persistent reduced maternal blood flow to the placenta, resulting in persistent hypoxia and increased angiogenesis, with a constellation of pathologic features of maternal vascular malperfusion atlate gestation. Wilm’s tumor gene (WT1) expression appears to be central to steroid and peptide hormonal actions in early pregnancy, and vascular regeneration/restoration after pregnancy. Conclusions: Spiral artery remodeling at early pregnancy leads to hypoxia with vascular transformation, and the establishment of uteroplacental circulation results in relief of hypoxia. The hypoxia–re-oxygenation sequence may provide insights into the mechanism of normal fetal/placental development and associated pregnancy complications, such as preeclampsia.