Dexamethasone Induces Germ Cell Apoptosis in the Human Fetal Ovary
| Autor: | Gabriel Livera, Virginie Rouiller-Fabre, Alexandra Benachi, Marine Poulain, Clotilde Duquenne, Nelly Frydman, Thierry N’Tumba-Byn, René Habert |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Clinical Biochemistry Apoptosis Cell Count Context (language use) Ovary Biology Biochemistry Dexamethasone Fetus Oogonia Organ Culture Techniques Receptors Glucocorticoid Endocrinology Glucocorticoid receptor Pregnancy Internal medicine medicine Humans Congenital adrenal hyperplasia Glucocorticoids Adrenal Hyperplasia Congenital Virilization Biochemistry (medical) Gene Expression Regulation Developmental medicine.disease Virilism Proto-Oncogene Proteins c-kit medicine.anatomical_structure Female medicine.symptom Germ cell medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 97:E1890-E1897 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2012-1681 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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