title: Glucocorticoid exposure altered angiogenic factor expression via Akt/mTOR pathway in rat placenta.
abstract: During pregnancy, glucocorticoids (GCs) are used for fetal lung maturation in women at risk of preterm labor. Exogenous GCs do not have exclusively beneficial effects and repeated use of GCs remains controversial. It has been observed that GC exposed rats have smaller placentas and intrauterine growth retarded fetuses. In this study, we questioned whether or not glucocorticoids effect placental angiogenesis mechanisms. One of the most important signaling pathways among several downstream of VEGFR-2 is PI3K/Akt which subsequently activates the mammalian target of rapamycin. Therefore, we hypothesized that overexposure to GCs may adversely affect placental angiogenesis mechanisms by regulating pro-angiogenic factors and their receptors via Akt/mTOR pathway. According to our results Dexamethasone, a synthetic glucocorticoid, administration led to a decrease in VEGF, PIGF expression during pregnancy. VEGFR2 expression was first decreased at gestational day 14 and afterwards increased at gestational days 16, 18 and 20 in rat placentas. These results are in accordance with the reduced phosphorylation of Akt, 4EBP1 and p70S6K. Dexamethasone injection also resulted in a reduction of VEGF, VEGFR1, and VEGFR2 mRNA expression at gestational days 14 and 20, but PIGF mRNA expression was not altered. Growth retarded fetuses seen in Dexamethasone treated pregnancies, may be a result of altered angiogenic factor expression of the placenta mediated via altered mTOR pathway signaling.
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey.
authors.forename: Asli
authors.initials: A
authors.lastname: Ozmen
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey.
authors.forename: Gozde
authors.initials: G
authors.lastname: Unek
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: Busra
authors.initials: B
authors.lastname: Cetinkaya
authors.affiliation: Department of Biochemistry, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Avcil
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Akdeniz University, 07070 Antalya, Turkey. Electronic address: korgun@akdeniz.edu.tr.
authors.forename: Emin Türkay
authors.initials: ET
authors.lastname: Korgun
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010920:Placenta / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D042501:Angiogenic Proteins; D005938:Glucocorticoids; D003907:Dexamethasone; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Akt/mTOR; Angiogenesis; Glucocorticoid; Placenta; Rat