Inverted formin 2 regulates intracellular trafficking, placentation, and pregnancy outcome

Healthy pregnancy depends on proper placentation-including proliferation, differentiation, and invasion of trophoblast cells-which, if impaired, causes placental ischemia resulting in intrauterine growth restriction and preeclampsia. Mechanisms regulating trophoblast invasion, however, are unknown....

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Bibliographic Details
Published in:eLife 2018-01, Vol.7
Main Authors: Lamm, Katherine Young Bezold, Johnson, Maddison L, Baker Phillips, Julie, Muntifering, Michael B, James, Jeanne M, Jones, Helen N, Redline, Raymond W, Rokas, Antonis, Muglia, Louis J
Format: Article
Language:English
Subjects:
Achievement tests
Analysis
Angiogenesis
Animal experimentation
Animals
Cell Biology
Cell Differentiation
Cell Movement
Cell proliferation
Dams
Developmental Biology
Embryo
extravillous trophoblast invasion
Families & family life
Female
Fetal development
Fetuses
Genes
Gestational hypertension
Hospitals
Hypertension
INF2
Infants
Intracellular
intrauterine growth restriction
Ischemia
Mammals
Mice
Mice, Knockout
Microfilament Proteins - deficiency
Microfilament Proteins - metabolism
Natural gas transmission
Nutrition
Perfusion
Phenotypes
Physicians
Placenta
placental insufficiency
Placentation
Polymerization
Pre-eclampsia
Preeclampsia
Pregnancy
Pregnancy Outcome
Pregnant women
Premature birth
Proteins
Scientific equipment industry
Scientists
Software
Trophoblasts
Trophoblasts - physiology
Veins & arteries
Velocity
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Summary:Healthy pregnancy depends on proper placentation-including proliferation, differentiation, and invasion of trophoblast cells-which, if impaired, causes placental ischemia resulting in intrauterine growth restriction and preeclampsia. Mechanisms regulating trophoblast invasion, however, are unknown. We report that reduction of ( alters intracellular trafficking and significantly impairs invasion in a model of human extravillous trophoblasts. Furthermore, global loss of in mice recapitulates maternal and fetal phenotypes of placental insufficiency. dams have reduced spiral artery numbers and late gestational hypertension with resolution following delivery. fetuses are growth restricted and demonstrate changes in umbilical artery Doppler consistent with poor placental perfusion and fetal distress. Loss of increases fetal vascular density in the placenta and dysregulates trophoblast expression of angiogenic factors. Our data support a critical regulatory role for in trophoblast invasion-a necessary process for placentation-representing a possible future target for improving placentation and fetal outcomes.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.31150