Faculty Collaboration Database

Inverted formin 2 regulates intracellular trafficking, placentation, and pregnancy outcome. Elife 2018 Jan 08;7

Date

01/09/2018

Pubmed ID

29309034

Pubmed Central ID

PMC5758111

DOI

10.7554/eLife.31150

Scopus ID

2-s2.0-85042088382 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

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 Inverted formin 2 (INF2) alters intracellular trafficking and significantly impairs invasion in a model of human extravillous trophoblasts. Furthermore, global loss of Inf2 in mice recapitulates maternal and fetal phenotypes of placental insufficiency. Inf2^-/- dams have reduced spiral artery numbers and late gestational hypertension with resolution following delivery. Inf2^-/- fetuses are growth restricted and demonstrate changes in umbilical artery Doppler consistent with poor placental perfusion and fetal distress. Loss of Inf2 increases fetal vascular density in the placenta and dysregulates trophoblast expression of angiogenic factors. Our data support a critical regulatory role for INF2 in trophoblast invasion-a necessary process for placentation-representing a possible future target for improving placentation and fetal outcomes.

Author List

Lamm KYB, Johnson ML, Baker Phillips J, Muntifering MB, James JM, Jones HN, Redline RW, Rokas A, Muglia LJ

MESH terms used to index this publication - Major topics in bold

Animals
Cell Differentiation
Cell Movement
Female
Mice
Mice, Knockout
Microfilament Proteins
Placentation
Pregnancy
Pregnancy Outcome
Trophoblasts