Journal
BRAIN RESEARCH
Volume 1433, Issue -, Pages 29-37Publisher
ELSEVIER
DOI: 10.1016/j.brainres.2011.11.030
Keywords
Endocrine disruptor; 17-alpha-ethinylestradiol; GnRH-1 neuron; Development; Mouse; Neurogenesis
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Funding
- European FF program [2004-513953]
- French ANR [AF08 CES 011]
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To evaluate the potentially disrupting effects of environmental estrogens on neuroendocrine networks controlling reproduction, we studied the impact of the pharmaceutical product 17-alpha-ethinylestradiol (EE2) on gonadotropin-releasing hormone (GnRH-1) neuron development in mouse embryo. Pregnant mice were treated per os with EE2 at 0.01, 0.1 or 1 mu g/kg/day, between embryonic days 10.5 (E10.5) and E13.5, a period during which GnRH-1 neurons are generated and start their intra-nasal migration. Embryos at E13.5 were examined and processed for GnRH-1 immunohistochemistry. Immunopositive neurons were counted all along their migratory path. A short oral administration of environmentally relevant doses of EE2 to pregnant mice had a significant impact on whole embryo development, leading to a limited but significant growth retardation. The total number of GnRH-1 neurons was statistically significantly increased in a dose-dependent manner. The repartition of GnRH-1 neurons along their migratory path was not affected by EE2 treatment. These results suggest an impact of environmental EE2 concentrations on embryonic GnRH-1 development through a modulation of neurogenesis and/or apoptosis. (C) 2011 Elsevier B.V. All rights reserved.
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