Folic acid prevents congenital malformations in the offspring of diabetic mice

Kaori Oyama, Yoshihisa Sugimura, Takashi Murase, Akira Uchida, Shizu Hayasaka, Yutaka Oiso, Yoshiharu Murata

研究成果: Article

32 引用 (Scopus)

抄録

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 malformations 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.

元の言語English
ページ(範囲)29-37
ページ数9
ジャーナルEndocrine Journal
56
発行部数1
DOI
出版物ステータスPublished - 24-03-2009

Fingerprint

Folic Acid
Neural Tube Defects
Fetal Diseases
Homocysteine
Apoptosis
Control Groups
Mothers
Rhombencephalon
Organogenesis
In Situ Nick-End Labeling
Streptozocin
Fetus
Embryonic Structures
Body Weight
Glucose
Pregnancy
Incidence

All Science Journal Classification (ASJC) codes

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

これを引用

Oyama, Kaori ; Sugimura, Yoshihisa ; Murase, Takashi ; Uchida, Akira ; Hayasaka, Shizu ; Oiso, Yutaka ; Murata, Yoshiharu. / Folic acid prevents congenital malformations in the offspring of diabetic mice. :: Endocrine Journal. 2009 ; 巻 56, 番号 1. pp. 29-37.
@article{ca7a4907ff6343f3877468b9294f9f05,
title = "Folic acid prevents congenital malformations in the offspring of diabetic mice",
abstract = "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 malformations 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.",
author = "Kaori Oyama and Yoshihisa Sugimura and Takashi Murase and Akira Uchida and Shizu Hayasaka and Yutaka Oiso and Yoshiharu Murata",
year = "2009",
month = "3",
day = "24",
doi = "10.1507/endocrj.K08E-180",
language = "English",
volume = "56",
pages = "29--37",
journal = "Endocrine Journal",
issn = "0918-8959",
publisher = "Japan Endocrine Society",
number = "1",

}

Oyama, K, Sugimura, Y, Murase, T, Uchida, A, Hayasaka, S, Oiso, Y & Murata, Y 2009, 'Folic acid prevents congenital malformations in the offspring of diabetic mice', Endocrine Journal, 巻. 56, 番号 1, pp. 29-37. https://doi.org/10.1507/endocrj.K08E-180

Folic acid prevents congenital malformations in the offspring of diabetic mice. / Oyama, Kaori; Sugimura, Yoshihisa; Murase, Takashi; Uchida, Akira; Hayasaka, Shizu; Oiso, Yutaka; Murata, Yoshiharu.

:: Endocrine Journal, 巻 56, 番号 1, 24.03.2009, p. 29-37.

研究成果: Article

TY - JOUR

T1 - Folic acid prevents congenital malformations in the offspring of diabetic mice

AU - Oyama, Kaori

AU - Sugimura, Yoshihisa

AU - Murase, Takashi

AU - Uchida, Akira

AU - Hayasaka, Shizu

AU - Oiso, Yutaka

AU - Murata, Yoshiharu

PY - 2009/3/24

Y1 - 2009/3/24

N2 - 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 malformations 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.

AB - 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 malformations 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.

UR - http://www.scopus.com/inward/record.url?scp=62549091501&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62549091501&partnerID=8YFLogxK

U2 - 10.1507/endocrj.K08E-180

DO - 10.1507/endocrj.K08E-180

M3 - Article

C2 - 18781038

AN - SCOPUS:62549091501

VL - 56

SP - 29

EP - 37

JO - Endocrine Journal

JF - Endocrine Journal

SN - 0918-8959

IS - 1

ER -