title: Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring.
abstract: The migration of gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode to the preoptic area (POA) from embryonic day 13 is important for successful reproduction during adulthood. Whether maternal glucocorticoid exposure alters GnRH neuronal morphology and number in the offspring is unknown. This study determines the effect of maternal dexamethasone (DEX) exposure on enhanced green fluorescent protein (EGFP) driven by GnRH promoter neurons (TG-GnRH) in transgenic rats dual-labelled with GnRH immunofluorescence (IF-GnRH). The TG-GnRH neurons were examined in intact male and female rats at different postnatal ages, as a marker for GnRH promoter activity. Pregnant females were subcutaneously injected with DEX (0.1 mg/kg) or vehicle daily during gestation days 13-20 to examine the number of GnRH neurons in P0 male offspring. The total number of TG-GnRH neurons and TG-GnRH/IF-GnRH neuronal ratio increased from P0 and P5 stages to P47-52 stages, suggesting temporal regulation of GnRH promoter activity during postnatal development in intact rats. In DEX-treated P0 males, the number of IF-GnRH neurons decreased within the medial septum, organum vasculosom of the lamina terminalis (OVLT) and anterior hypothalamus. The percentage of TG-GnRH neurons with branched dendritic structures decreased in the OVLT of DEX-P0 males. These results suggest that maternal DEX exposure affects the number and dendritic development of early postnatal GnRH neurons in the OVLT/POA, which may lead to altered reproductive functions in adults.
authors.affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, Petaling Jaya, 46150, Selangor, Malaysia.
authors.forename: Wei Ling
authors.initials: WL
authors.lastname: Lim
authors.forename: Tomoko
authors.initials: T
authors.lastname: Soga
authors.forename: Ishwar S
authors.initials: IS
authors.lastname: Parhar
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D019076:Transgenes / Q000235:genetics
chemical_list: D049452:Green Fluorescent Proteins; D007987:Gonadotropin-Releasing Hormone; D003907:Dexamethasone