title: Early dexamethasone treatment induces placental apoptosis in sheep.
abstract: Glucocorticoid treatment given in late pregnancy in sheep resulted in altered placental development and function. An imbalance of placental survival and apoptotic factors resulting in an increased rate of apoptosis may be involved. We have now investigated the effects of dexamethasone (DEX) in early pregnancy on binucleate cells (BNCs), placental apoptosis, and fetal sex as a determinant of these responses. Pregnant ewes carrying singleton fetuses (n = 105) were randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 49, intramuscular injections of 0.14 mg/kg ewe weight per 12 hours over 48 hours) at 40 to 41 days of gestation (dG). Placentomes were collected at 50, 100, 125, and 140 dG. At 100 dG, DEX in females reduced BNC numbers, placental antiapoptotic (proliferating cell nuclear antigen), and increased proapoptotic factors (Bax, p53), associated with a temporarily decrease in fetal growth. At 125 dG, BNC numbers and apoptotic markers were restored to normal. In males, ovine placental lactogen-protein levels after DEX were increased at 50 dG, but at 100 and 140 dG significantly decreased compared to controls. In contrast to females, these changes were independent of altered BNC numbers or apoptotic markers. Early DEX was associated with sex-specific, transient alterations in BNC numbers, which may contribute to changes in placental and fetal development. Furthermore, in females, altered placental apoptosis markers may be involved.
authors: Division of Experimental Obstetrics, Department of Obstetrics, Study Group Perinatal Programming, Campus Virchow, Berlin, Germany thorsten.braun@charite.de.
authors: Thorsten
authors: T
authors: Braun
authors: Division of Experimental Obstetrics, Department of Obstetrics, Study Group Perinatal Programming, Campus Virchow, Berlin, Germany Department of Obstetrics and Gynecology, The Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia, China.
authors: Wenbin
authors: W
authors: Meng
authors: Division of Experimental Obstetrics, Department of Obstetrics, Study Group Perinatal Programming, Campus Virchow, Berlin, Germany Department of Obstetrics and Gynecology, Hangzhou First People's Hospital, Zhejiang, China.
authors: Hongkai
authors: H
authors: Shang
authors: School of Women's and Infants' Health, King Edward Memorial Hospital, The University of Western Australia, Crawley, Western Australia, Australia.
authors: Shaofu
authors: S
authors: Li
authors: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.
authors: Deborah M
authors: DM
authors: Sloboda
authors: Division of Experimental Obstetrics, Department of Obstetrics, Study Group Perinatal Programming, Campus Virchow, Berlin, Germany.
authors: Loreen
authors: L
authors: Ehrlich
authors: Division of Experimental Obstetrics, Department of Obstetrics, Study Group Perinatal Programming, Campus Virchow, Berlin, Germany.
authors: Karolin
authors: K
authors: Lange
authors: Division of Experimental Obstetrics, Department of Obstetrics, Study Group Perinatal Programming, Campus Virchow, Berlin, Germany Department of Obstetrics and Gynecology, Linyi People's Hospital, Lanshan, China.
authors: Huaisheng
authors: H
authors: Xu
authors: Division of Experimental Obstetrics, Department of Obstetrics, Study Group Perinatal Programming, Campus Virchow, Berlin, Germany.
authors: Wolfgang
authors: W
authors: Henrich
authors: Division of Experimental Obstetrics, Department of Obstetrics, Study Group Perinatal Programming, Campus Virchow, Berlin, Germany.
authors: Joachim W
authors: JW
authors: Dudenhausen
authors: Division of Experimental Obstetrics, Department of Obstetrics, Study Group Perinatal Programming, Campus Virchow, Berlin, Germany.
authors: Andreas
authors: A
authors: Plagemann
authors: School of Women's and Infants' Health, King Edward Memorial Hospital, The University of Western Australia, Crawley, Western Australia, Australia.
authors: John P
authors: JP
authors: Newnham
authors: School of Women's and Infants' Health, King Edward Memorial Hospital, The University of Western Australia, Crawley, Western Australia, Australia Department of Physiology Obstetrics and Gynecology, at the University of Toronto, Toronto, Canada Faculty of Health Sciences, Simon Fraser University Vancouver, Vancouver, Canada.
authors: John R G
authors: JR
authors: Challis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000633:toxicity*; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D020567:Fetal Weight / Q000187:drug effects; D005865:Gestational Age; D005938:Glucocorticoids / Q000633:toxicity*; D008297:Male; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012737:Sex Factors; D012756:Sheep; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D003907:Dexamethasone
keywords: apoptopic markers; binucleate cell; glucocorticoid; placenta; placental lactogen