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. Author manuscript; available in PMC: 2017 Feb 1.
Published in final edited form as: Am J Obstet Gynecol. 2015 Sep 30;214(2):192–202. doi: 10.1016/j.ajog.2015.09.082

Figure 1. Maternal diabetes induces yolk sac vasculopathy via reduction of HIF-1α.

Figure 1

Under normoxic conditions, specific prolylhydroxylases (PHDs) induce oxygen-dependent hydroxylation of HIF-1α. HIF-1α then binds to the von Hippel-Lindau tumor suppressor protein (pVHL), which acts as an E3 ubiquitin ligase and targets HIF-1α for proteasomal degradation. Under hypoxic conditions, HIF-1α translocates to the nucleus, engages HIF-1β, and forms the HIF-1 complex that initiates transcription of downstream genes, including VEGFs. Maternal diabetes reduces HIF-1α levels by enhancing its degradation. The lack of HIF-1α leads to the development of extensive vascular defects, which is similar to diabetic yolk sac vasculopathy.