Hyperglycemia results in significant pathophysiological changes of placental spiral artery remodeling and angiogenesis, further contributing to congenital defects

Together, these results suggest that gestational diabetes perturbs proper placental development and function, specifically spiral artery remodeling and angiogenesis, thereby negatively impacting embryonic development.

Streptozotocin was used to induce gestational diabetes in mice. In this model, hyperglycemia was established at embryonic day 3.5 (E3.5). Pregnancy mass was collected at E10.5, E12.5, E14.5, and E16.5 for different assessments.

Both placental and embryonic weights were found to be significantly elevated at E16.5. At E14.5, a significantly larger junctional zone with increased number of glycogen trophoblasts was found in the placentas from hyperglycemic pregnancies (HG group) compared to the placentas from normoglycemic pregnancies (NG group). Importantly, the HG placenta exhibited decreased trophoblast giant cell (TGC) association and TUNEL+ cells, and increased expression of α-SMA on the spiral artery, suggesting arterial remodeling was impacted. Moreover, the interhemal membrane of the labyrinth layer, was found to be thicker in the HG placentas. Furthermore, hyperglycemia resulted in more offspring congenital defects, which were associated with a thicker interhemal membrane. Conclusions: Together, these results suggest that gestational diabetes perturbs proper placental development and function, specifically spiral artery remodeling and angiogenesis, thereby negatively impacting embryonic development.