title: Dexamethasone exposure affects paraventricular nucleus and pituitary corticotrophs in female rat fetuses: An unbiased stereological and immunohistochemical study.
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 0.5mg 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.
authors.affiliation: Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 despota Stefana Blvd., 11060 Belgrade, Serbia. Electronic address: manojlo@ibiss.bg.ac.rs.
authors.forename: Milica
authors.initials: M
authors.lastname: Manojlović-Stojanoski
authors.affiliation: Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 despota Stefana Blvd., 11060 Belgrade, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Nestorović
authors.affiliation: Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 despota Stefana Blvd., 11060 Belgrade, Serbia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Trifunović
authors.affiliation: Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 despota Stefana Blvd., 11060 Belgrade, Serbia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Ristić
authors.affiliation: Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 despota Stefana Blvd., 11060 Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Jarić
authors.affiliation: Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 despota Stefana Blvd., 11060 Belgrade, Serbia.
authors.forename: Branko
authors.initials: B
authors.lastname: Filipović
authors.affiliation: Institute for Biological Research "Siniša Stanković", University of Belgrade, 142 despota Stefana Blvd., 11060 Belgrade, Serbia.
authors.forename: Verica
authors.initials: V
authors.lastname: Milošević
mesh_terms: D000818:Animals; D052680:Corticotrophs / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis*; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000254:growth & development; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000254:growth & development; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone
keywords: ACTH; CRH; Dexamethasone; Fetus; Paraventricular nucleus; Programming