Trisomy 21 is associated with variable defects in cytotrophoblast differentiation along the invasive pathway

American Journal of Medical Genetics. Part a
Alexi WrightS J Fisher

Abstract

Aneuploid cells in the placenta are associated with poor pregnancy outcomes, but the mechanisms are unclear. Here, we examined the cytotrophoblast (CTB) differentiation pathway that leads to uterine invasion in pregnancies complicated by trisomy 21 (T21) as compared with their normal counterparts. Surprisingly, we observed a wide spectrum of T21 effects. Morphologically, some samples appeared near normal, while others had extensive fibrinoid deposition and apoptosis of CTBs at the maternal-fetal interface (confirmed by TUNEL labeling). At a molecular level, the cells' expression of stage-specific molecules was variably misregulated. At one end of the spectrum, samples with less apoptosis had relatively normal staining patterns. At the other end, samples with extensive apoptosis showed significantly decreased staining for these antigens. Additional studies confirmed that the effects we observed had functional consequences, because the cells exhibited marked phenotypic alterations in vitro, including a large increase in MMP-9 production, which distinguishes the effects of T21 on CTBs from those of preeclampsia. The morphologic, phenotypic, and functional differences among CTBs from pregnancies complicated by T21 illustrate the im...Continue Reading

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Citations

Sep 17, 2004·The Journal of Clinical Investigation·Kristy Red-HorseSusan J Fisher
Aug 13, 2013·The Journal of Clinical Investigation·Yan ZhouSusan J Fisher
Sep 21, 2011·Proteome Science·Wendy E HeywoodNeil D Avent
Feb 10, 2007·Reproductive Biology and Endocrinology : RB&E·Laura LunghiFortunato Vesce
Sep 21, 2005·Genetics·Randall J RoperRoger H Reeves
May 23, 2014·Annual Review of Genomics and Human Genetics·Anthony R GreggMary E Norton
Sep 23, 2014·Current Hypertension Reports·Anjali AcharyaTanvi Rege
Dec 19, 2007·Biochimica Et Biophysica Acta·Satoko AsaiYoshiko Shimizu
Aug 7, 2007·Fertility and Sterility·Yasushi SasakiLaurence A Cole
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Dec 30, 2014·Reproductive Biology and Endocrinology : RB&E·Marie Clémence LeguyJean Guibourdenche
Aug 16, 2005·American Journal of Obstetrics and Gynecology·Tuangsit WataganaraDiana W Bianchi
Aug 25, 2012·Biochimica Et Biophysica Acta·Jiska JebbinkCarrie Ris-Stalpers
Nov 6, 2015·Archives of Gynecology and Obstetrics·Christel Eckmann-ScholzAli Salmassi
Jul 29, 2006·Prenatal Diagnosis·Paul J YongWendy Robinson
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Feb 13, 2020·Reproductive Sciences·Daisy Leon-MartinezKatherine Bianco
Aug 13, 2011·Journal of Clinical Pathology·Laura AvaglianoAnna Maria Marconi
Feb 20, 2018·Experimental and Therapeutic Medicine·Lingyu Hu, Changju Zhou
Sep 28, 2021·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Karampreet KaurLisa C Zuckerwise

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