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Dexamethasone exposure affects paraventricular nucleus and pituitary corticotrophs in female rat fetuses: An unbiased stereological and immunohistochemical study
Institution:1. Faculty of Veterinary Sciences, Islamic Azad University, Science and Research Campus, Tehran, Iran;2. Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran;3. Department of Physiology, Faculty of Veterinary Sciences, Islamic Azad University, Science and Research Campus, Tehran, Iran;4. Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran;5. Department of Pathology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran;6. Department of Histology, Faculty of Veterinary Sciences, Urmia University, Urmia, Iran;1. Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC;2. Department of Health Psychology, Chang Jung Christian University, Tainan 71101, Taiwan, ROC;3. Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, Tainan 70101, Taiwan, ROC;1. Shaanxi Institute of Pediatric Diseases, The Affiliated Children Hospital of Xi’an Jiaotong University College of Medicine, Shaanxi 86-710003, PR China;2. Department of Neonatology, The First Affiliated Hospital of Xi’an Jiaotong University, Shaanxi 86-710061, PR China;3. The Affiliated Children Hospital of Xi’an Jiaotong University College of Medicine, Shaanxi 86-710003, PR China;4. Shaanxi Province Biomedicine Key Laboratory, College of Life Sciences, Northwest University, Shaanxi 86-710069, PR China;1. Institute of Behavioral Medicine, National Cheng Kung University College of Medicine, Tainan 701, Taiwan, ROC;2. Department of Health Psychology, Chang Jung Christian University, Tainan 711, Taiwan, ROC;3. Department of Physiology and Pharmacology, Chang-Gung University, Taoyuan 333, Taiwan, ROC
Abstract:The hypothalamic paraventricular nucleus (PVN) drives the stress response by activating the hypothalamo-pituitary-adrenal (HPA) axis, particularly vulnerable to glucocorticoid exposure during development. To evaluate the effects of fetal dexamethasone (Dx) exposure on the stereological features of PVN and HPA axis activity in female rat fetuses, pregnant rats received 0.5 mg Dx/kg/b.w./day on days 16, 17 and 18 of pregnancy and 21-day-old fetuses were obtained; controls received the same volume of saline. In an unbiased stereological approach, Cavalieri’s principle and an optical fractionator were used for estimating volume and total cell number of the PVN, respectively. The intensity of corticotropin-releasing hormone (CRH) immunoreactivity in the median eminence (ME) was determined by CRH optical density and the adrenocorticotropic hormone (ACTH) relative fluorescence signal intensity (RIF) in pituitary corticotrophs was measured using Image J. Significant reductions (p < 0.05) in PVN volume and cell number were found in fetuses exposed to Dx. Additionally, CRH optical density in the ME and ACTH RIF (p < 0.05) in the corticotrophs were decreased. The established results suggest that the reduced number of cells in the PVN after maternal Dx administration negatively affects the CRH content in the ME and the ACTH quantity in pituitary corticotrophs in near-term fetuses.
Keywords:Paraventricular nucleus  Fetus  Dexamethasone  Programming  CRH  ACTH
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