title: Trisomy 21 is associated with variable defects in cytotrophoblast differentiation along the invasive pathway.
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 importance of the interplay between fetal/placental genotype and maternal influences on pregnancy outcome. Furthermore, our data may explain why a significant number of these pregnancies end in spontaneous abortion while others survive to term.
authors.affiliation: University of Pennsylvania Medical School, Philadelphia, PA, USA.
authors.forename: Alexi
authors.initials: A
authors.lastname: Wright
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jingly Fung
authors.initials: JF
authors.lastname: Weier
authors.forename: Eduardo
authors.initials: E
authors.lastname: Caceres
authors.forename: Mirhan
authors.initials: M
authors.lastname: Kapidzic
authors.forename: Takako
authors.initials: T
authors.lastname: Tabata
authors.forename: Madelyn
authors.initials: M
authors.lastname: Kahn
authors.forename: Carl
authors.initials: C
authors.lastname: Nash
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Fisher
mesh_terms: D000022:Abortion, Spontaneous; D000941:Antigens / Q000032:analysis; D017209:Apoptosis; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics*; D004314:Down Syndrome / Q000235:genetics* / Q000503:physiopathology*; D010064:Embryo Implantation; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006801:Humans; D010641:Phenotype; D010929:Placentation; D014327:Trophoblasts / Q000166:cytology*
chemical_list: D000941:Antigens