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    Sun, Wu-Ping Zhai, Ming-Zhu Li, Da Zhou, Yiming Chen, Na-Na Guo, Ming and Zhou, Shi-Sheng 2016. Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels. Clinical Nutrition,

    Xue, Jing and Ideraabdullah, Folami Y. 2016. An assessment of molecular pathways of obesity susceptible to nutrient, toxicant and genetically induced epigenetic perturbation. The Journal of Nutritional Biochemistry, Vol. 30, p. 1.

    Vaiman, Daniel 2015. Human Placental Trophoblasts.

    Zhou, Shi-Sheng Li, Da and Zhou, Yiming 2015. Management of nicotinamide N-methyltransferase overexpression: inhibit the enzyme or reduce nicotinamide intake?. Diabetologia, Vol. 58, Issue. 9, p. 2191.


Maternal nicotinamide supplementation causes global DNA hypomethylation, uracil hypo-incorporation and gene expression changes in fetal rats

  • Yan-Jie Tian (a1), Ning Luo (a1), Na-Na Chen (a1), Yong-Zhi Lun (a1), Xin-Yi Gu (a2), Zhi Li (a1), Qiang Ma (a2) and Shi-Sheng Zhou (a1)
  • DOI:
  • Published online: 10 February 2014

Recent evidence shows that excess nicotinamide can cause epigenetic changes in developing rats. The aim of the present study was to investigate the effects of maternal nicotinamide supplementation on the fetus. Female rats were randomised into four groups fed a standard chow diet (control group) or diets supplemented with 1 g/kg of nicotinamide (low-dose group), 4 g/kg of nicotinamide (high-dose group) or 4 g/kg of nicotinamide plus 2 g/kg of betaine (betaine group) for 14–16 d before mating and throughout the study. Fetal tissue samples were collected on the 20th day of pregnancy. Compared with the control group, the high-dose group had a higher fetal death rate, and the average fetal body weight was higher in the low-dose group but lower in the high-dose group. Nicotinamide supplementation led to a decrease in placental and fetal hepatic genomic DNA methylation and genomic uracil contents (a factor modifying DNA for diversity) in the placenta and fetal liver and brain, which could be completely or partially prevented by betaine. Moreover, nicotinamide supplementation induced tissue-specific alterations in the mRNA expression of the genes encoding nicotinamide N-methyltransferase, DNA methyltransferase 1, catalase and tumour protein p53 in the placenta and fetal liver. High-dose nicotinamide supplementation increased fetal hepatic α-fetoprotein mRNA level, which was prevented by betaine supplementation. It is concluded that maternal nicotinamide supplementation can induce changes in fetal epigenetic modification and DNA base composition. The present study raises the concern that maternal nicotinamide supplementation may play a role in the development of epigenetic-related diseases in the offspring.

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*Corresponding authors: S.-S. Zhou, fax +86 411 87402053, email; Q. Ma, email;
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