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Study on the mechanism of fetal dismorphogenesis from mothers with diabetes mellitus using rat whole-embryo culture system.

Research Project

Project/Area Number 05671408
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionKurume University

Principal Investigator

HASUO Yasuyuki (1995)  Kurume University School of Medicine, Research Associate, 医学部, 助手 (00189515)

片瀬 剛 (1994)  久留米大学, 医学部, 助手 (40204424)

哲翁 正博 (1993)  久留米大学, 医学部, 助教授 (30167522)

Co-Investigator(Kenkyū-buntansha) YAMANAKA Hideki  Kurume University School of Medicine, Research Associate, 医学部, 助手 (00248444)
NAKASHIMA Hiroshi  Kurume University School of Medicine, Research Associate, 医学部, 助手 (90248443)
KATAOKA Akio  Kurume University School of Medicine, Research Associate, 医学部, 助手 (40194758)
KATASE Tsuyoshi  Kurume University School of Medicine, Research Associate, 医学部, 助手 (40204424)
蓮尾 泰之  久留米大学, 医学部, 助手 (00189515)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
KeywordsDiabetes mellitus / Pregnancy / Fetal malformation / Rat whole-embryo culture / Hyperglycemia / Hypoglycemia / Hyperketonemia / 糖尿病合併妊婦 / 奇形 / 胚培養 / 先天奇形 / 細胞接着分子
Research Abstract

Infants of diabetic mothers have an increased incidence of congenital malformations. Although the management of diabetic pregnancy has improved, the incidence of congenital malformations has not been changed over the past two decades, which are the main cause of perinatal death in infants from diabetic mothers. Since teratogenic factors associated with diabetes are diverse and complicated, the effect of each factor on the fetus is difficult to evaluate in an in vivo experiment. Attempts were therefore made to establish an in vitro rat whole embryo culture system which allowed us to make evaluation of the effects of specific materials on the fetus during the organogenic periods. Whole embryo culture was performed according to the method of New et al. On day 9 of pregnancy, Wister strain rat's embryos were explanted into culture medium and were cultured at 37゚C for 48 h with rotation at 60 rpm in our original rotation cultivator. After 48-h culture, embryonal growth was assessed by direc … More t measurement of crown-to-rump length (CRL) and somitogenesis in embryos.
Major and minor malformations were characterized by neural leisons and by less severe extraneural lesions, respectively. The effects of various factors being generated by abnormal carbohydrate metabolism such as hyperglycemia, hypoglycemia and hyperketonemia were then studied by adding various concentrations of glucose and beta hydrozybutylate into culture medium. The embryos from the high glucose medium (300mg/dl*) had significantly shorter CRL and fewer somites. The incidence of major and minor malformations increased as the glucose concentration increased (300mg/dl*). Hypoglycemia for 48 h (50mg/dl of glucose) exerted embryopathic effects on rat embryos. Embryos exposed to hypoglycemia during the first 24 h were more vulnerable to growth retardation and dysmorphogenesis than those exposed for another 24 h.
The effects were enhanced by a flucation of glucose concentration in the culture medium. The 48 h exposure to hyperketonemia (6mM* of beta hydroxybutylate) exhibited growth retardation and major and minor malformations. The coexistence of high glucose and beta hydroxybutylate acted synergistically to enhance the adverse effects on fetus. In conclusion, these findings indicate that the higher and lower concentrations of glucose, and ketone bodies are some of the substantial components which influence embryo growth, development and abnormalitis. Less

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Misuzu Tomonari: "Effects fo hypoglycemia on early embryogenesis in rat whole-embryo culture" Journal of Maternal-Fetal Investigation. 4. 241-246 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Misuzu Tomonari, Masahiro Tetsuo, Tsuyoshi Katase, Michiaki Yakushizi, Teiji Hamada: "Effects of hypoglycemia on early embryogenesis in rat whole-embryo culture system." Journal of Maternal-Fetal Investigation. 4. 241-246 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Misuzu Tomonari: "Effects of hypoglycemia on early embryogenesis in rat whole-embryo culture system" Journal of Maternal-Fetal Investigation. 4. 241-246 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] M.Tomonari,M.Tetsuo et al: "Effectsof hypoglycemia on early embryogenesis in rat whole-embryo culture system" Journal of Maternal Fetal Investigation accepted for publication. (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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