Document Detail


Dexamethasone Induces Germ Cell Apoptosis in the Human Fetal Ovary.
MedLine Citation:
PMID:  22802086     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Context:The 21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia. Pregnant women presenting a risk of genetic transmission may be treated with synthetic glucocorticoids such as dexamethasone (DEX) to prevent female fetus virilization.Objective:The aim of this study was to assess the potential deleterious effects of DEX exposure on fetal ovarian development.Settings:Human fetal ovaries, ranging from 8-11 weeks after fertilization, were harvested from material available after legally induced abortions. They were cultured in the absence or presence of DEX (2, 10, or 50 μm) over 14 d, and histological analyses were performed.Results:The glucocorticoid receptor NR3C1 was present and the signaling pathway active in the fetal ovary as demonstrated by the expression of NR3C1 target genes, such as PLZF and FKBP5, in response to DEX exposure. DEX decreased germ cell density at the 10 and 50 μm doses. Exposure to DEX, even at the highest dose, did not change oogonial proliferation as monitored by 5-bromo-2'-deoxyuridine incorporation and significantly increased the apoptotic rate, detected with cleaved caspase 3 staining. Interestingly, the expression of the prosurvival gene KIT was significantly decreased in the presence of DEX during the course of the culture.Conclusion:We have demonstrated for the first time that in vitro exposure to high doses of DEX impairs human fetal oogenesis through an increase in apoptosis. These data are of high importance, and additional epidemiological studies are required to investigate the female fertility of those women who have been exposed to DEX during fetal life.
Authors:
Marine Poulain; Nelly Frydman; Clotilde Duquenne; Thierry N'tumba-Byn; Alexandra Benachi; René Habert; Virginie Rouiller-Fabre; Gabriel Livera
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-16
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  -     ISSN:  1945-7197     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Commissariat à l'Energie Atomique (M.P., N.F., C.D., T.N'T.-B., R.H., V.R.-F., G.L.), Direction des sciences du vivant/Institut de radiobiologie cellulaire et moléculaire/Service cellules souches et radiation/ Laboratoire de Développement des Gonades (LDG), Unité Cellules Souches et Radiation; Université Paris-Diderot (C.D., T.N'T.-B., R.H., V.R.-F., G.L.), Sorbonne Paris Cité, LDG, Unité Mixte de Recherche (UMR)-967; Institut National de la Santé et de la Recherche Médicale Unité 967 (M.P., N.F., C.D., N.N'T.-B., R.H., V.R.-F., G.L.); and Université Paris-Sud (M.P., N.F.), LDG, UMR-967, F-92265 Fontenay aux Roses, France; and Assistance Publique-Hôpitaux de Paris, Unité de Biologie de la Reproduction (A.B., M.P., N.F.) and Service de Gynécologie-Obstétrique et Médecine de la Reproduction (A.B.), Hôpital Antoine Béclère, and Université Paris-Sud (A.B.), Clamart, F-92140, France.
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