The research article was published online in the international comprehensive biological journal biology Courtesy of Shanghai Ocean University
China News Network, March 7 (Reporter Xu Jing) Folic acid is a kind of B vitamin, and folic acid supplementation during pregnancy has become a consensus. So, isn't folic acid the more it is added, the better? Han Xuhui, a team of associate professor Zu Yao of the School of Fisheries and Life Sciences of Shanghai Ocean University, found that excessive supplementation with folic acid or insufficient intake of folic acid may lead to abnormal cardiac development in zebrafish embryos.
Recently, a research paper titled "Precise Dose of Folic Acid Supplementation Is Essential for Embryonic Heart Development in Zebrafish" was published online in the international comprehensive biological journal Biology.
This study is the first to elucidate the mechanism of action of folic acid on early heart development and provides a scientific basis for the rational dosage of folic acid supplementation. At the same time, Zu Yao's team also constructed zebrafish mutants with abnormal folic acid metabolism, providing a new biological model for the study of folate metabolism.
In order to simulate the development environment of human fetuses in the mother's body and study how folic acid metabolism affects the development of the embryonic heart, Zu Yao's team selected a model organism zebrafish with the advantages of short growth cycle, large spawning volume and transparent embryo to carry out experiments.
The zebrafish that will "glow" has become the "weapon" of the team's research. This is a special, fluorescent zebrafish that facilitates the observation of the development of folic acid-treated embryos. Under microscopic specific excitation light, this zebrafish cardiovascular endothelial cells show red fluorescence and cardiomyocytes appear green fluorescence.
Zu Yao has long been committed to the research of CRISPR gene editing technology. Courtesy of Shanghai Ocean University
Han Xuhui, the first author of the paper and a master's student at the School of Fisheries and Life Sciences of Shanghai Ocean University, said: "Specifically labeled fluorescence can help us see organ development more clearly and intuitively. ”
The study found that abnormal cardiac cyclization occurred in the folic acid antagonist group (i.e., inhibition of folic acid metabolism) three days after the birth of zebrafish, while the atrium and ventricles of zebrafish embryos with excessive folic acid were elongated. The team came up with experimental results that both folate deficiency and excess can cause abnormal heart development in zebrafish embryos.
"In addition to insufficient folate intake, the cause of the body's lack of folic acid is also affected by genetic factors," Zu Yao explains, "different methylenetetrahydrofolate reductase (MTHFR) genotypes, which can cause differences in folate metabolism between different populations." "People with MTHFR genotype are CC types have normal folate activation capacity, while people with CT or TT types have different degrees of folate metabolism defects.
The abnormal folic acid metabolism caused by the reduction genetic defect, Zu Yao's team also wanted to "find the answer" in the zebrafish. They use the lab's "housekeeping skills" – CRISPR gene editing technology. This "gene scissor hand" technique enables precise target editing of gene base sequences.
Zu Yao has long been committed to the research of CRISPR gene editing technology. Using the "gene scissor hand", the team successfully constructed a zebrafish fish system with a variety of mutants such as congenital heart disease, chronic heart failure, dilated cardiomyopathy, including a variety of mutant fish that accurately simulated folic acid deficiency models, which can be used as an ideal biological model for human diseases.
From experiments in zebrafish, the team concluded that excessive folic acid supplementation or insufficient folate metabolism has a negative effect on the early development of the organism, and that folic acid has a dose-dependent effect on the development of the organism. Based on the conclusion, Zu Yao's team suggested that it is not good to supplement folic acid too little, too much is not good, it needs to be "just right", and it should also be through genetic testing to understand its own folate metabolism capacity.
It is reported that in the future, Zu Yao's team will combine the laboratory's expertise in microinjection, in situ hybridization and other molecular genetic mechanism research methods, explain the pathogenesis of disease and continue to screen and discover relevant therapeutic target drugs and compounds through high-throughput drug screening technology, providing a pioneering theoretical basis and experimental new discoveries for the research of human health medicine. (End)