1995 Fiscal Year Final Research Report Summary
Study on the mechanism of fetal dismorphogenesis from mothers with diabetes mellitus using rat whole-embryo culture system.
| Project/Area Number |
05671408
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kurume University |
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Principal Investigator |
HASUO Yasuyuki Kurume University School of Medicine, Research Associate, 医学部, 助手 (00189515)
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| 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)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Diabetes mellitus / Pregnancy / Fetal malformation / Rat whole-embryo culture / Hyperglycemia / Hypoglycemia / Hyperketonemia |
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| 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
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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
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