title: Determination of PCNA, cyclin D3, p27, p57 and apoptosis rate in normal and dexamethasone-induced intrauterine growth restricted rat placentas.
abstract: Intrauterine growth restriction (IUGR) is a major clinical problem, which causes perinatal morbidity and mortality. One of the reasons for IUGR is abnormal placentation. In rats, fetal-placental exposure to maternally administered glucocorticoids decreases birth weight and placental weight. Proper placental development depends on the proliferation and differentiation of trophoblasts. Our knowledge about the mitotic regulators that play key roles in synchronizing these events is limited. Also the mechanisms underlying the placental growth inhibitory effects of glucocorticoids have not been elucidated. The aim of this study was to investigate the immunolocalization, mRNA and protein levels of proliferating cell nuclear antigen (PCNA), cyclin D3, p27 and p57 in normal and dexamethasone-induced IUGR Wistar rat placentas by reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry and Western blot. We also compared apoptotic cell numbers at the light microscopic level via terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) and transmission electron microscopy. Glucocorticoid levels were higher in IUGR rats than in control rats after 60 and 120min of injection. We showed reduced gene and protein expressions of PCNA and cyclin D3 and increased expressions of p27 and p57 in IUGR placentas compared to control placentas. Apoptotic cell number was higher in the placentas of the IUGR group. In brief we found that maternal dexamethasone treatment led to a shift from cell proliferation to apoptosis in IUGR placentas. Dexamethasone induced placental and embryonal abnormalities which could be associated with reduced expressions of PCNA and cyclin D3, increased expressions of p27 and p57 and increased rate of apoptosis in IUGR placentas.
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey; Department of Biophysics, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Er
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey.
authors.forename: Nuray
authors.initials: N
authors.lastname: Acar
authors.affiliation: Department of Biochemistry, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey.
authors.forename: Dijle
authors.initials: D
authors.lastname: Kipmen-Korgun
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey.
authors.forename: Ciler
authors.initials: C
authors.lastname: Celik-Ozenci
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey.
authors.forename: Ismail
authors.initials: I
authors.lastname: Ustunel
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey.
authors.forename: Mevlut
authors.initials: M
authors.lastname: Asar
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey. Electronic address: korgun@akdeniz.edu.tr.
authors.forename: Emin Turkay
authors.initials: ET
authors.lastname: Korgun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D056743:Cyclin D3 / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000378:metabolism*; D003907:Dexamethasone / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; C534698:Ccnd3 protein, rat; C493962:Cdkn1b protein, rat; D056743:Cyclin D3; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018809:Proliferating Cell Nuclear Antigen; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003907:Dexamethasone
keywords: Apoptosis; Cyclin D3; PCNA; Rat placenta; p27; p57