If a mother with diabetes drinks green tea during pregnancy, could it improve her child’s development? For years, pregnant women have been advised to take probiotics and antioxidants, such as folic acid, to help improve pregnancy outcomes. However, the precise way these supplements work continues to be up for debate. Now, epigenetic evidence is mounting in regard to the benefits of certain antioxidants and the potential underlying biological mechanisms. New research published in the American Journal of Obstetrics & Gynecology explores whether a polyphenol, Epigallocatechin gallate (EGCG), found in green tea has a therapeutic effect and can reduce defects of a developing embryo caused by a mother’s hyperglycemia.
Diabetes is becoming increasingly prevalent in society and the number of women of reproductive age who have diabetes is expected to double by 2030 to 120 million. Diabetes during pregnancy can cause a number of abnormal birth defects, including neural tube defects. These defects are common complex congenital malformations of the central nervous system. Maternal diabetes has been shown to induce cellular stress, which leads to apoptosis and, ultimately, deformity of the neural tube in offspring.
The lead researchers Jianxiang Zhong, PhD and Cheng Xu, PhD worked with their team to determine whether EGCG could reduce neural tube defects caused by maternal diabetes. In previous studies, EGCG has been linked to cancer suppression via inhibition of DNA methyltransferases (DNMTs), which are enzymes that catalyze the popular epigenetic mechanism known as DNA methylation. DNA methylation suppresses gene expression. Therefore, by inhibiting DNMTs, the expression of genes linked to tumor suppression was increased. DNA methylation has also been shown to disrupt the folate metabolic pathway and cause neural tube defects. Based off this information, Dr. Zhong and Dr. Xu investigated whether DNMT activity and DNA methylation levels were linked to EGCG consumption and could improve the early development of children being born to diabetic mothers.
The team of scientists used a diabetic mouse model to measure DNMT activity and global DNA methylation changes caused by administering EGCG to diabetic and non-diabetic pregnant mice via drinking water. DNMT activity in embryos from diabetic dams was measured using a fluorometric DNMT activity/inhibition assay kit from EpiGentek. The EpiQuik DNMT Activity/Inhibition Assay Ultra Kit (Fluorometric) measures DNA methyltransferase activity or inhibition at extremely fast speeds on a 96-stripwell microplate. They found that EGCG was able to inhibit the expression of DNA methyltransferases that increased as a result of maternal diabetes.
In addition, the researchers used EpiGentek’s MethylFlash Methylated DNA 5-mC Quantification Kit for absorbance-based quantitation of global DNA methylation in the embryos. Consistent with the levels of DNMTs that they discovered, the researchers found that global DNA methylation levels were increased “in embryos from the diabetic group, compared with the nondiabetic group, and Epigallocatechin gallate treatment blocked maternal diabetes-increased global DNA methylation levels.”
Furthermore, the group performed methylation-specific PCR (MS-PCR) and uncovered increased DNA methylation levels of CpG islands of genes Grhl3, Pax3, and Tulp3, in embryos from diabetic mothers. These genes are all necessary for neural tube closure.
Overall, these results hint that ingesting polyphenol EGCG, which makes up 30% of the solids in green tea, could lead to healthy offspring even if a mother is diabetic. In addition to reducing the risk of neural tube defects, EGCG may also be able to correct epigenetic alterations linked to other structural birth defects, including congenital heart defects. However, additional research is needed on how EGCG interacts in the human body and whether or not this could be an effective epigenetic treatment. According to the researchers, further research that focuses on ways to reduce DNA hypermethylation and oxidative stress in embryos “may be critical to reducing the risk of neural tube defects in the offspring of diabetic mothers.”
Source: Zhong, J., Xu, C., Reece, E.A., Yang, P. (2016). The green tea polyphenol EGCG alleviates maternal diabetes–induced neural tube defects by inhibiting DNA hypermethylation. American Journal of Obstetrics & Gynecology, in press.