Regulation of hypoxia inducible factors (HIF) in hypoxia and normoxia during placental development.
During the first trimester of pregnancy the human placenta develops in an hypoxic environment caused by the occlusion of uterine spiral arterioles by extravillous trophoblasts (EVT). This period of low oxygen tension is crucial for successful pregnancy. In low oxygen environments, Hypoxia Inducible Factors (HIF) are the main regulators in the transcription of a number of genes. Target genes can induce anaerobic processes, reducing oxygen consumption, or promote angiogenesis, which establishes and enhances the vascular environment. The HIFs can function throughout all stages of placental differentiation and growth both in normal and pathological pregnancies (compromised by hypoxia/ischemia). Interestingly, HIFs respond to a multitude of changes during pregnancy, including 1) low oxygen, 2) renin-angiotensin system (RAS), 3) cytokines, and 4) growth factors, all of which regulate placental function. This review explores oxygen-dependent and oxygen-independent regulation and the role of HIF in placental development and differentiation.
Patel
J
J
School of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital, Herston, Queensland 4029, Australia. jatin.patel@qimr.edu.au
Landers
K
K
Mortimer
R H
RH
Richard
K
K
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000502:physiology; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy; D012097:Repressor Proteins; D015398:Signal Transduction; D000099162:Endothelial PAS Domain-Containing Protein 1
D051017:Apoptosis Regulatory Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012097:Repressor Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1; C116973:HIF3A protein, human