title: Gestational loss and growth restriction by angiogenic defects in placental growth factor transgenic mice.
abstract: OBJECTIVE
  Angiogenesis is an important biological process during development, reproduction, and in immune responses. Placental growth factor (PlGF) is a member of vascular endothelial growth factor that is critical for angiogenesis and vasculogenesis. We generated transgenic mice overexpressing PlGF in specifically T cells using the human CD2-promoter to investigate the effects of PlGF overexpression.
  
  
  RESULTS
  Transgenic mice were difficult to obtain owing to high lethality; for this reason, we investigated why gestational loss occurred in these transgenic mice. Here, we report that placenta detachment and inhibition of angiogenesis occurred in PlGF transgenic mice during the gestational period. Moreover, even when transgenic mice were born, their growth was restricted.
  
  
  CONCLUSIONS
  Conclusively, PlGF overexpression prevents angiogenesis by inhibiting Braf, extracellular signal-regulated kinase activation, and downregulation of HIF-1α in the mouse placenta. Furthermore, it affected regulatory T cells, which are important for maintenance of pregnancy.
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Min-Cheol
authors.initials: MC
authors.lastname: Kang
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Seo Jin
authors.initials: SJ
authors.lastname: Park
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Hei Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Jinhee
authors.initials: J
authors.lastname: Lee
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Yu
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Ki Beom
authors.initials: KB
authors.lastname: Bae
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Ji
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Si Jun
authors.initials: SJ
authors.lastname: Park
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Jain
authors.initials: J
authors.lastname: Jeong
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Woo Young
authors.initials: WY
authors.lastname: Jang
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Jung-Hak
authors.initials: JH
authors.lastname: Kim
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Hyun-Shik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Gyeongsin
authors.initials: G
authors.lastname: Park
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Yeon Sik
authors.initials: YS
authors.lastname: Choo
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.).
authors.forename: Je-Yoel
authors.initials: JY
authors.lastname: Cho
authors.affiliation: From the School of Life Sciences and Biotechnology (M.K., S.J.P., H.J.K., J.L., D.H.Y., K.B.B., Y.R.J., S.J.P., J.J., W.Y.J., J.-H.K., D.-S.L., H.-S.L., S.L., S.H.K., M.O.K., Z.Y.R.), Department of Food Science and Nutrition (M.S.C.), and School of Biology (Y.S.C.), Kyungpook National University, Daegu, Korea; Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea (G.P.); and Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul, Korea (J.-Y.C.). jaewoong64@hanmail.net.
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
mesh_terms: D000818:Animals; D001835:Body Weight; D018801:CD2 Antigens / Q000235:genetics; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005313:Fetal Death / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005865:Gestational Age; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008098:Litter Size; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018801:CD2 Antigens; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: BRAF kinases; extracellular signal-regulated kinases; miscarriage; placenta growth factor; regulatory T-cells