Document Detail

Human placental development is impaired by abnormal human chorionic gonadotropin signaling in trisomy 21 pregnancies.
MedLine Citation:
PMID:  17690166     Owner:  NLM     Status:  MEDLINE    
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.
Guillaume Pidoux; Pascale Gerbaud; Olivier Marpeau; Jean Guibourdenche; Fatima Ferreira; Josette Badet; Danièle Evain-Brion; Jean-Louis Frendo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-09
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-17     Completed Date:  2007-11-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5403-13     Citation Subset:  AIM; IM    
Institut National de la Santé et de la Recherche Médicale, Unité 767, Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75270, Paris, France.
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MeSH Terms
Cells, Cultured
Chorionic Gonadotropin / physiology*,  secretion
Down Syndrome / embryology*,  pathology,  physiopathology*
Models, Biological
Pregnancy Complications / physiopathology
Receptors, LH / genetics,  metabolism
Signal Transduction / physiology
Trophoblasts / metabolism,  pathology,  secretion
Reg. No./Substance:
0/Chorionic Gonadotropin; 0/Receptors, LH

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