Folic Acid Prevents Congenital Malformations in the Offspring of Diabetic Mice
Folic Acid Prevents Congenital Malformations in the Offspring of Diabetic Mice
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DOI：
10.1507/endocrj.k08e-180
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发表时间：
2009-02-01
影响因子：
2
通讯作者：
Murata, Yoshiharu
中科院分区：
文献类型：
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作者：
Oyama, Kaori;Sugimura, Yoshihisa;Murata, Yoshiharu
众所周知，产妇糖尿病会导致各种先天性畸形。虽然有许多报道称妊娠期服用叶酸可降低神经管缺陷（NTDs）等出生缺陷的风险，但尚未对叶酸对糖尿病胚胎病的预防作用进行精确分析。在这项研究中，我们使用糖尿病小鼠模型分析了FA对先天性畸形（包括NTDs，心血管和骨骼畸形）的预防作用。雌性小鼠用链脲佐菌素致高血糖，然后进行交配。妊娠糖尿病小鼠在妊娠第6 ~ 10天每天给予FA （3 mg/kg体重）或生理盐水。妊娠第18天，检查胎儿是否有先天性畸形。FA不影响血糖水平。在DM对照组中，ntd、心血管和骨骼畸形的发生率分别为28.4%、28.5%和29.7%。fa处理组相应比例分别降至6.0%、2.5%和12.5%。全贴壁TUNEL结果显示，DM对照组胚胎后脑区凋亡增加，FA处理后细胞凋亡减少。与非DM组相比，DM对照组妊娠9.5时母体血浆同型半胱氨酸水平显著降低，FA治疗无显著影响。这些结果表明，FA对包括NTDs、心血管和骨骼畸形在内的多种糖尿病胚胎病变有预防作用，并提示其作用与同型半胱氨酸代谢无关，可能通过减少器官发生过程中的异常凋亡介导。
It is well known that maternal diabetes causes various congenital malformations. Although there are many reports that folic acid (FA) administration in pregnancy reduces the risk of birth defects including neural tube defects (NTDs), a precise analysis on the preventive effect of FA against diabetic embryopathy has not been done yet. In this study, we analyzed the preventive effects of FA on congenital malfomations including NTDs, cardiovascular, and skeletal malformations using a diabetic mouse model. Female mice were rendered hyperglycemic by streptozotocin and then mated. Pregnant diabetic mice were treated daily with FA (3 mg/kg body weight) or saline between gestational days (GD) 6 and 10. On GD 18, fetuses were examined for congenital malformations. FA did not affect plasma glucose levels. In the DM control group, the incidence of NTDs, cardiovascular, and skeletal malformations was 28.4%, 28.5%, and 29.7%, respectively. In the FA-treated group, the corresponding proportions reduced to 6.0%, 2.5% and 12.5%, respectively. A whole-mount TUNEL revealed an increased apoptosis in the hindbrain region of embryos from DM control group on day 9.5, and the apoptosis was decreased by FA treatment. Maternal plasma homocysteine levels on GD 9.5 were significantly lowered in DM control group compared with those in non-DM group, and FA treatment did not show a significant effect. These results indicate that FA is effective for the prevention of various diabetic embryopathy including NTDs, cardiovascular, and skeletal malformations, and Suggested that this effect is independent from homocysteine metabolism and possibly mediated by decreasing the abnormal apoptosis during organogenesis.