title: Maternal exposure to 17-alpha-ethinylestradiol alters embryonic development of GnRH-1 neurons in mouse.
abstract: To evaluate the potentially disrupting effects of environmental estrogens on neuroendocrine networks controlling reproduction, we studied the impact of the pharmaceutical product 17-α-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 μg/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.
authors.affiliation: Université de Tours, Physiologie de la Reproduction et des Comportements, IFR135, UMR 6175 INRA, CNRS, Haras Nationaux, 37380 Nouzilly, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Pillon
authors.forename: Virginie
authors.initials: V
authors.lastname: Cadiou
authors.forename: Leslie
authors.initials: L
authors.lastname: Angulo
authors.forename: Anne Hélène
authors.initials: AH
authors.lastname: Duittoz
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects* / Q000502:physiology; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011498:Protein Precursors / Q000378:metabolism*
chemical_list: D011498:Protein Precursors; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone; D004997:Ethinyl Estradiol