China News Service, Shanghai, March 7th (Reporter Xu Jing) Folic acid is one of the B vitamins, and folic acid supplementation during pregnancy has become a consensus.
So, is the more folic acid supplement the better?
The team of Associate Professor Zu Yao, School of Fisheries and Life Sciences, Shanghai Ocean University, Han Xuhui and others found that excessive folic acid supplementation or insufficient folic acid intake may lead to abnormal heart development in zebrafish embryos.
Recently, a research article entitled "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 a reasonable supplemental dose of folic acid.
At the same time, Zu Yao's team also constructed a zebrafish mutant with abnormal folic acid metabolism, providing a new biological model for the study of folic acid metabolism.
In order to simulate the developmental environment of the human fetus in the mother's body and study how folic acid metabolism affects the development of the embryonic heart, Zu Yao's team selected the model organism zebrafish, which has the advantages of short growth cycle, large egg production, and transparent embryos.
The "glowing" zebrafish has become the "sharp weapon" of the team's research.
This is a special, fluorescent zebrafish that facilitates observation of the entire developmental process of folic acid-treated embryos.
Under microscope-specific excitation light, the zebrafish cardiovascular endothelial cells fluoresce red and cardiomyocytes fluoresce green.
Zu Yao has long been committed to the research of CRISPR gene editing technology.
Photo courtesy of Shanghai Ocean University
Han Xuhui, the first author of the paper and a postgraduate student at the School of Fisheries and Life Sciences, Shanghai Ocean University, said: "Specifically labeled fluorescence can help us see the development of organs more clearly and intuitively."
The study found that abnormal cardiac cyclization occurred in the folate antagonist group (i.e., inhibition of folic acid metabolism) three days after birth, while the atria and ventricles of zebrafish embryos in the experimental group with excess folic acid were elongated.
The team found experimental results that both folate deficiency and excess can cause abnormal heart development in zebrafish embryos.
"In addition to insufficient folic acid intake, the cause of folic acid deficiency in the body is also affected by genetic factors," Zu Yao explained, "Different methylenetetrahydrofolate reductase (MTHFR) genotypes will cause folic acid metabolism in different groups. There are differences." Among them, people with MTHFR genotype CC have normal folic acid activation ability, while people with CT or TT genotype have different degrees of folic acid metabolism defects.
To restore the abnormal folic acid metabolism caused by genetic defects, Zu Yao's team also wanted to "find the answer" in zebrafish.
They used the lab's "housekeeping skill" -- CRISPR gene-editing technology.
This "gene scissors-hand" technology can precisely target and edit gene base sequences.
Yao Zu has long been devoted to the research of CRISPR gene editing technology.
Using the "gene scissors hand", the team successfully constructed a variety of mutant zebrafish lines such as congenital heart disease, chronic heart failure, dilated cardiomyopathy, etc., including accurate simulation of folic acid deficiency models and other mutant fish, which can be used as human Ideal biological model of disease.
From the zebrafish experiments, the team concluded that excessive folic acid supplementation or insufficient folic acid metabolism had a negative effect on the early development of the organism, and that folic acid had a dose-dependent effect on the development of the organism.
Based on the conclusion, Zu Yao's team suggested that supplementing too little folic acid is not good, and too much is not good. It needs to be "just right", and genetic testing should also be used to understand one's own folic acid metabolism.
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 to explain the pathogenic mechanism of the disease and continue to screen and discover related treatments through high-throughput drug screening technology. Targeted drugs and compounds provide pioneering theoretical foundations and new experimental discoveries for the study of human health medicine.
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