Heather I Levin1, Chantae S Sullivan-Pyke1, Virginia E Papaioannou2, Ronald J Wapner3, Jan K Kitajewski4, Carrie J Shawber5, Nataki C Douglas6. 1. Department of Obstetrics and Gynecology, Columbia University Medical Center, 622 West 168th St., New York, NY 10032, USA. 2. Department of Genetics and Development, Columbia University Medical Center, 701 West 168th St., New York, NY 10032, USA. 3. Department of Obstetrics and Gynecology, Columbia University Medical Center, 622 West 168th St., New York, NY 10032, USA; Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Columbia University Medical Center, 630 West 168th St., New York, NY 10032, USA. 4. Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Columbia University Medical Center, 630 West 168th St., New York, NY 10032, USA; Department of Physiology and Biophysics, University of Illinois, 835 S. Wolcott Avenue, Room E202, Chicago, IL 60612, USA. 5. Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Columbia University Medical Center, 630 West 168th St., New York, NY 10032, USA; Department of Surgery, College of Physicians and Surgeons, Columbia University Medical Center, 630 West 168th St., New York, NY 10032, USA. 6. Department of Obstetrics and Gynecology, Division of Reproductive Sciences, Columbia University Medical Center, 630 West 168th St., New York, NY 10032, USA; Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Columbia University Medical Center, 622 West 168th St., New York, NY 10032, USA. Electronic address: nd2058@cumc.columbia.edu.
Abstract
INTRODUCTION: Murine placentation requires trophoblast Notch2, while the Notch ligand, JAGGED1, is reduced in invasive trophoblasts from women with preeclampsia. However, the placental cells with active Notch signaling and expression of other Notch proteins and ligands in placentation have yet to be defined. We sought to identify endothelial cell and trophoblast subtypes with canonical Notch signaling in the decidua and placenta and correlate this to expression of Notch proteins and ligands. METHODS: Notch reporter transgenic mice were used to define canonical Notch activity and immunofluorescence staining performed to characterize expression of Notch1, 2, 3, 4 and ligands, Delta-like 4 (Dll4) and Jagged1 (Jag1) during early placentation and in the mature placenta. RESULTS: Notch signaling is active in maternal and fetal endothelial cells and trophoblasts during early placentation and in the mature placenta. Dll4, Jag1, Notch1, and Notch4 are expressed in maternal vasculature in the decidua. Dll4, Jag1 and Notch1 are expressed in fetal vasculature in the labyrinth. Dll4, Notch2 and Notch4 are co-expressed in the ectoplacental cone. Notch2 and Notch4 are expressed in parietal-trophoblast giant cells and junctional zone trophoblasts with active canonical Notch signaling and in labyrinthine syncytiotrophoblasts and sinusoidal-trophoblast giant cells. DISCUSSION: Canonical Notch activity and distinct expression patterns for Notch proteins and ligands was evident in endothelium and trophoblasts, suggesting Notch1, Notch2, Notch4, Dll4, and Jag1 have distinct and overlapping functions in placentation. Characterization of Notch signaling defects in existing mouse models of preeclampsia may shed light on the role of Notch in developing the preeclampsia phenotype.
INTRODUCTION:Murine placentation requires trophoblast Notch2, while the Notch ligand, JAGGED1, is reduced in invasive trophoblasts from women with preeclampsia. However, the placental cells with active Notch signaling and expression of other Notch proteins and ligands in placentation have yet to be defined. We sought to identify endothelial cell and trophoblast subtypes with canonical Notch signaling in the decidua and placenta and correlate this to expression of Notch proteins and ligands. METHODS:Notch reporter transgenic mice were used to define canonical Notch activity and immunofluorescence staining performed to characterize expression of Notch1, 2, 3, 4 and ligands, Delta-like 4 (Dll4) and Jagged1 (Jag1) during early placentation and in the mature placenta. RESULTS:Notch signaling is active in maternal and fetal endothelial cells and trophoblasts during early placentation and in the mature placenta. Dll4, Jag1, Notch1, and Notch4 are expressed in maternal vasculature in the decidua. Dll4, Jag1 and Notch1 are expressed in fetal vasculature in the labyrinth. Dll4, Notch2 and Notch4 are co-expressed in the ectoplacental cone. Notch2 and Notch4 are expressed in parietal-trophoblast giant cells and junctional zone trophoblasts with active canonical Notch signaling and in labyrinthine syncytiotrophoblasts and sinusoidal-trophoblast giant cells. DISCUSSION: Canonical Notch activity and distinct expression patterns for Notch proteins and ligands was evident in endothelium and trophoblasts, suggesting Notch1, Notch2, Notch4, Dll4, and Jag1 have distinct and overlapping functions in placentation. Characterization of Notch signaling defects in existing mouse models of preeclampsia may shed light on the role of Notch in developing the preeclampsia phenotype.
Authors: David G Simmons; David R C Natale; Valerie Begay; Martha Hughes; Achim Leutz; James C Cross Journal: Development Date: 2008-04-30 Impact factor: 6.868
Authors: Jennifer L Sones; Audrey A Merriam; Angelina Seffens; Dex-Ann Brown-Grant; Scott D Butler; Anna M Zhao; Xinjing Xu; Carrie J Shawber; Jennifer K Grenier; Nataki C Douglas Journal: FASEB J Date: 2018-01-08 Impact factor: 5.191
Authors: Barry E Perlman; Audrey A Merriam; Alexander Lemenze; Qingshi Zhao; Salma Begum; Mohan Nair; Tracy Wu; Ronald J Wapner; Jan K Kitajewski; Carrie J Shawber; Nataki C Douglas Journal: Reproduction Date: 2021-05-14 Impact factor: 3.906
Authors: Jacinta I Kalisch-Smith; Emily C Morris; Mary A A Strevens; Andia N Redpath; Kostantinos Klaourakis; Dorota Szumska; Jennifer E Outhwaite; Xin Sun; Joaquim Miguel Vieira; Nicola Smart; Sarah De Val; Paul R Riley; Duncan B Sparrow Journal: Front Genet Date: 2022-01-19 Impact factor: 4.599
Authors: Yichao Wang; Ruixue Yang; Xiaolin Wang; Hongfei Ci; Lei Zhou; Bo Zhu; Shiwu Wu; Danna Wang Journal: Medicine (Baltimore) Date: 2018-12 Impact factor: 1.817
Authors: Nicole M Marchetto; Salma Begum; Tracy Wu; Valerie O'Besso; Christina C Yarborough; Nuriban Valero-Pacheco; Aimee M Beaulieu; Jan K Kitajewski; Carrie J Shawber; Nataki C Douglas Journal: Int J Mol Sci Date: 2020-09-05 Impact factor: 5.923