Figure 2.

Fetal insulinemia and altered angiogenesis in fetoplacental endothelium from gestational diabetes mellitus. With the progression of pregnancy up to the 40th weeks of gestation, the maternal glycaemia increases, and could reach supraphysiological levels in pregnancies where the mother is diagnosed with gestational diabetes mellitus. The maternal hyperglycaemia results in increased fetal glycaemia from about the 5th week of gestation (dotted line), a condition resulting in a supraphysiological increase of fetal insulinemia from the 12th week of gestation. Increased fetal insulinemia results in altered placental vascular development and growth leading to angiogenesis alterations (Placental vasculogenesis and angiogenesis). Thus, an adverse fetal outcome is seen as a result of abnormal angiogenesis. Cell signaling mechanisms involved in this phenomenon include altered expression and/or activity of several molecules that are responsive to insulin (IR-A, MMPs, cadherin, b-catenin). Equally, a low oxygen level at the beginning of pregnancy increases the expression of proangiogenic growth factors (VEGF, PlGF, IGF, FGF-2) and increased (GRP78, CHOP, IRE-1α, ATF6, PERK) or reduced (AMPK) expression and/or activity. Composed from information reported by Babawale et al. (2000), Jirkovská et al. (2002), Easwaran et al. (2003), Baumüller et al. (2015), Westermeier et al. (2015b).