title: Human placental development is impaired by abnormal human chorionic gonadotropin signaling in trisomy 21 pregnancies.
abstract: Placental development is markedly abnormal in women bearing a fetus with trisomy 21, with defective syncytiotrophoblast (ST) formation and function. The ST occurs from cytotrophoblast (CT) fusion and plays an essential role by secreting human chorionic gonadotropin (hCG), which is essential to placental development. In trisomy of chromosome 21 (T21) pregnancies, CTs do not fuse and differentiate properly into STs, leading to the secretion of an abnormal and weakly bioactive hCG. In this study we report for the first time, a marked decrease in the number of mature hCG receptor (LH/CG-R) molecules expressed at the surface of T21-affected CTs. The LH/CG-R seems to be functional based on sequencing that revealed no mutations or deletions and binding of recombinant hCG as well as endogenous hCG. We hypothesize that weakly bioactive hCG and lower LH/CG-R expression may be involved in the defect of ST formation. Interestingly, the defective ST formation is mimicked in normal CT cultures by using LH/CG-R small interfering RNA, which result in a lower hCG secretion. Furthermore, treatment of T21-affected CTs with recombinant hCG overcomes in vitro the T21 phenotype, allowing CTs to fuse and form a large ST. These results illustrate for the first time in trisomy 21 pathology, how abnormal endogenous hCG signaling impairs human placental development.
authors: Institut National de la Santé et de la Recherche Médicale, Unité 767, Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75270, Paris, France.
authors: Guillaume
authors: G
authors: Pidoux
authors: Pascale
authors: P
authors: Gerbaud
authors: Olivier
authors: O
authors: Marpeau
authors: Jean
authors: J
authors: Guibourdenche
authors: Fatima
authors: F
authors: Ferreira
authors: Josette
authors: J
authors: Badet
authors: Danièle
authors: D
authors: Evain-Brion
authors: Jean-Louis
authors: JL
authors: Frendo
mesh_terms: D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000502:physiology*; D004314:Down Syndrome / Q000196:embryology* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008954:Models, Biological; D010929:Placentation; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology
chemical_list: D006063:Chorionic Gonadotropin; D011974:Receptors, LH