Defect of syncytiotrophoblast formation and human chorionic gonadotropin expression in Down's syndrome.
The syncytiotrophoblast (ST) is a major component of the human placenta as it is involved in feto-maternal exchanges and the secretion of pregnancy-specific hormones. We have studied the formation and function of the ST in normal and trisomy 21 (T21)-affected placenta using the in vitro model of cytotrophoblast differentiation into ST. Cytotrophoblast cells were isolated from first trimester, second trimester and term placentae. In vitro cytotrophoblast cells isolated from normal placenta fused to form the ST. This was associated with an increase in the transcript levels and the secretion of human chorionic gonadotropin (hCG). However, the secretion of hCG decreased through pregnancy. In T21-affected placentae, we observed a defect (or a delay) in ST formation and a dramatic decrease in the synthesis and secretion of this hormone compared with cultured cells isolated from control age-matched placentae. These results were confirmed by a significant (P < 0.05) decrease in transcript levels of alpha and beta subunits of hCG in total homogenates of T21-affected placentae compared with controls. These results suggest a decrease in functional mass of ST in T21 placenta, and therefore a decrease in production of placental pregnancy-specific polypeptide hormones.
Massin
N
N
Institut National de la Santé et de la Recherche Médicale, U427, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, France.
Frendo
J L
JL
Guibourdenche
J
J
Luton
D
D
Giovangrandi
Y
Y
Muller
F
F
Vidaud
M
M
Evain-Brion
D
D
D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000096:biosynthesis* / Q000235:genetics; D002824:Chorionic Villi / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000032:analysis; D051180:Desmoplakins; D004314:Down Syndrome / Q000378:metabolism / Q000473:pathology*; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005865:Gestational Age; D015292:Glycoprotein Hormones, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D014404:Tubulin / Q000032:analysis
D018997:Chorionic Gonadotropin, beta Subunit, Human; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D015292:Glycoprotein Hormones, alpha Subunit; D012333:RNA, Messenger; D014404:Tubulin; D016650:Fluorescein-5-isothiocyanate