Trophoblast-Specific Expression of Hif-1α Results in Preeclampsia-Like Symptoms and Fetal Growth Restriction

Scientific Reports
Renee E AlbersThomas L Brown

Abstract

The placenta is an essential organ that is formed during pregnancy and its proper development is critical for embryonic survival. While several animal models have been shown to exhibit some of the pathological effects present in human preeclampsia, these models often do not represent the physiological aspects that have been identified. Hypoxia-inducible factor 1 alpha (Hif-1α) is a necessary component of the cellular oxygen-sensing machinery and has been implicated as a major regulator of trophoblast differentiation. Elevated levels of Hif-1α in the human placenta have been linked to the development of pregnancy-associated disorders, such as preeclampsia and fetal growth restriction. As oxygen regulation is a critical determinant for placentogenesis, we determined the effects of constitutively active Hif-1α, specifically in trophoblasts, on mouse placental development in vivo. Our research indicates that prolonged expression of trophoblast-specific Hif-1α leads to a significant decrease in fetal birth weight. In addition, we noted significant physiological alterations in placental differentiation that included reduced branching morphogenesis, alterations in maternal and fetal blood spaces, and failure to remodel the maternal sp...Continue Reading

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Citations

Mar 8, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jean-Sebastien WattezJianhua Shao
Apr 7, 2020·Hypertension·Kathryn L GatfordAlison S Care
May 12, 2020·Journal of Biomedical Science·Pai-Sheng ChenShaw-Jenq Tsai
Sep 22, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Arthur ColsonFrédéric Debiève
Apr 9, 2020·International Journal of Molecular Sciences·Miguel A OrtegaNatalio García-Honduvilla
Jun 20, 2020·American Journal of Respiratory and Critical Care Medicine·Kellen HirschSteven H Abman
Oct 20, 2020·Biology of Reproduction·Xiaotao BianYan-Ling Wang
Jan 8, 2021·International Journal of Molecular Sciences·Lin PengViktoria von Schönfeldt
Apr 4, 2021·Antioxidants·Xiang-Qun Hu, Lubo Zhang
Jun 3, 2021·Placenta·Emma Siragher, Amanda N Sferruzzi-Perri
Jun 15, 2021·Human Reproduction Update·John D Aplin, Carolyn J P Jones
Jul 20, 2021·Frontiers in Physiology·Christopher A WakerThomas L Brown
Oct 9, 2021·BMC Pregnancy and Childbirth·Michalina BralewskaAgata Sakowicz

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Datasets Mentioned

BETA
AB3792

Methods Mentioned

BETA
transgenic
protein assay
ELISA
gene knockout
Assay
Infection
periodic acid Schiff

Software Mentioned

NIH ImageJ
Prism
Image J

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