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2006 Fiscal Year Final Research Report Summary

An experimental and clinical study on the development of adult disease in offspring with intrauterine undernutrition

Research Project

Project/Area Number 17390450
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionMie University

Principal Investigator

SAGAWA Norimasa  Mie University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (00162321)

Co-Investigator(Kenkyū-buntansha) SUGIYAMA Takashi  Mie University, University Hospital, Associate Professor, 医学部附属病院, 助教授 (10263005)
TABATA Tsutomu  Mie University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (40252358)
ITOH Hiroaki  National Hospital Organization, Osaka National Hospital, Medical Doctor, 産婦人科, 医員 (70263085)
YURA Shigeo  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (60335289)
MASUZAKI Hiroaki  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (00291899)
Project Period (FY) 2005 – 2006
Keywordspregnancy / intrauterine nutrition / fetal growth restriction / leptin / adult disease / obesity / hypertension / rennin angiotensin system
Research Abstract

Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We established a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. In leptin deficient ob/ob mice, intrauterine undernutrition did not caused pronounced obesity on anHFD. However, artificial premature le … More ptin surge in early neonatal period of this ob./ob mice resulted in a significant obesity on an HFD.
Wild type UN offspring showed an increase in systolic blood pressure (8 weeks of age; wks, P<0.05 and 16 wks, P<0.01), perivascular fibrosis of the coronary artery (16 wks, P<0.05) and cardiomegaly (16 wks, P<0.01) and cardiomyocyte nlargement, concomitant with a significant augmentation of angiotensinogen (Ang, P<0.05) and endothelin-1 (ET-1, P<0.01) mRNA expression and a tendency of increase in both angiotensin II and ET-1 immunostaining in the left ventricles (16 wks)
These findings suggest that the premature leptin surge alters energy regulation by the hypothalamus and contributes to "developmental origins of health and diseases" and that fetal undernutrition activated the local cardiac angiotensin system associated bioactive substances, which contributed, at least partly, to the development of cardiac remodeling in later life, in concert with the effects of increase in blood pressure. Less

  • Research Products

    (13 results)

All 2007 2005

All Journal Article (12 results) Book (1 results)

  • [Journal Article] Undernutrition in utero augments systolic blood pressure and cardiac remodeling in adult mouse offspring : Possible involvement of local cardiac angiotentin systemin developing origins of cardiovascular disease.2007

    • Author(s)
      Makoto Kawamura, Hiroaki Itoh, Shigeo Yura, 他7名
    • Journal Title

      Endocrinology 148

      Pages: 1218-1225

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Analysis on the promoter region of human decidual prolactin gene in the progesterone-induced decidualization and cAMP induced decidualization of human endometrial stromal cells.2007

    • Author(s)
      Dang Fang Wang, Hiroyuki Minoura, Takashi Sugiyama, 他4名
    • Journal Title

      Molecular and Cellular Biochemistry (In press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Undernutrition in utero augments systolic blood pressure and cardiac remodeling in adult mouse offspring : Possible involvement of local cardiac angiotentin systemin developing origins of cardiovascular disease.2007

    • Author(s)
      Makoto Kawamura, Hiroaki Itoh, Shigeo Yura, et al.
    • Journal Title

      Endocrinology Vol. 148

      Pages: 1218-1225

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Analysis on the promoter region of human decidual prolactin gene in the progesterorie-induced decidualization and cAMP induced decidualization of human endometrial stromal cells.2007

    • Author(s)
      Dong Fang Wang, Hiroyuki Minoura, Takashi Sugiyama, et al.
    • Journal Title

      Mollecular and Cellular Biochemistry (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of premature leptin surge in obesity resulting from intrauterine undernutrition.2005

    • Author(s)
      Shigeo Yura, Hiroaki Itoh, Norimasa Sagawa, 他8名
    • Journal Title

      Cell Metabolism 1

      Pages: 371-378

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cyclic mechanical stretch augments hyaluronan production in cultured human uterine cervical fibroblast cells.2005

    • Author(s)
      Maki Takemura, Hiroaki Itoh, Norimasa Sagawa, 他7名
    • Journal Title

      Molecular Human Reproduction 11

      Pages: 659-665

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Simultaneous increases of leptin and gonadotropin-releasing hormone following exogenous estrogen administration in women with normally menstrual cycle.2005

    • Author(s)
      Kuo-Cherung Lin, Norimasa Sagawa, 他3名
    • Journal Title

      Endocrine Journal 52

      Pages: 449-454

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Experimental transplantation study for possible transformation of bone marrow cells in the mouse placenta.2005

    • Author(s)
      Kazuyo Kakui, Hiroaki Itoh, Norimasa Sagawa, 他3名
    • Journal Title

      Placenta 26

      Pages: 678-685

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Role of premature leptin surge in obesity resulting from intrauterine undernutrition.2005

    • Author(s)
      Shigeo Yura, Hiroaki Itoh, Norimasa Sagawa, et al.
    • Journal Title

      Cell Metabolism Vol.1

      Pages: 371-378

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cyclic mechanical stretch augments hyaluronan production in cultured human uterine cervical fibroblast cells.2005

    • Author(s)
      Maki Takemura, Hiroaki Itoh, Norimasa Sagawa, et al.
    • Journal Title

      Molecular Human Reproduction Vol. 11

      Pages: 659-665

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Simultaneous increases of leptin and gonadotropin-releasing hormone following exogenous estrogen administration in women with normally menstrual cycle.2005

    • Author(s)
      Kuo-Cherung Lin, Norimasa Sagawa, Hiroaki Itoh, et al.
    • Journal Title

      Endocrine Journal Vol. 52

      Pages: 449-454

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Experimental transplantation study for possible transformation of bone marrow cells in the mouse placenta.2005

    • Author(s)
      Kazuyo Kakui, Hiroaki Itoh, Norimasa Sagawa, et al.
    • Journal Title

      Placenta Vol. 26

      Pages: 678-685

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Placenta and Trophoblast-Endocrinological Aspect.In : Textbook of Perinatal Medicine (eds. A Kurjak, et al.)2007

    • Author(s)
      Norimasa Sagawa
    • Publisher
      Taylor & Francis(In press)
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2008-05-27  

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