scholarly journals Precise Dose of Folic Acid Supplementation Is Essential for Embryonic Heart Development in Zebrafish

Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 28
Author(s):  
Xuhui Han ◽  
Bingqi Wang ◽  
Dongxu Jin ◽  
Kuang Liu ◽  
Hongjie Wang ◽  
...  
Keyword(s):  
Folic Acid ◽  
Heart Development ◽  
Cardiac Development ◽  
Folic Acid Supplementation ◽  
Mthfr Gene ◽  
Folate Metabolism ◽  
Marker Genes ◽  
Zebrafish Embryos ◽  
Cardiovascular Development ◽  
Acid Supplementation

Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. Moreover, we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid and mthfr−/− mutant all gave rise to early pericardial edema and cardiac defect at 3 days post fertilization (dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5 dpf. The expression levels of cardiac marker genes hand2, gata4, and nppa changed in the abnormality of folate metabolism embryos and mthfr−/− mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. Furthermore, our results reveal that folic acid has a dose-dependent effect on early cardiac development. Precise dosage of folic acid supplementation is crucial for the embryonic development of organisms.

scholarly journals Folic Acid Exerts Dose-Dependent Biphasic Effects on Cardiac Development of Zebrafish Embryos

2021 ◽  
Author(s):  
Xuhui Han ◽  
Bingqi Wang ◽  
Hongjie Wang ◽  
Yao Zu
Keyword(s):  
Folic Acid ◽  
Methylenetetrahydrofolate Reductase ◽  
Cardiac Development ◽  
Mthfr Gene ◽  
Folate Metabolism ◽  
Marker Genes ◽  
Zebrafish Embryos ◽  
Cardiovascular Development ◽  
Knock Out ◽  
Dose Dependent

Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is significantly associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. And we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid, and mthfr-/- mutant all gave rise to early pericardial edema and cardiac defect at 3 days after fertilization(dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5dpf. The expression levels of cardiac marker genes hand2, gata4 and nppa changed in the abnormality of folate metabolism embryos and mthfr-/- mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. And our results reveal that folic acid has a dose-dependent biphasic effect on early cardiac development.

scholarly journals ZIP-5/bZIP transcription factor regulation of folate metabolism is critical for aging axon regeneration

2019 ◽  
Author(s):  
Vanisha Lakhina ◽  
Melanie McReynolds ◽  
Daniel T. Grimes ◽  
Joshua D. Rabinowitz ◽  
Rebecca D. Burdine ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Folic Acid ◽  
Axon Regeneration ◽  
Folic Acid Supplementation ◽  
Folate Metabolism ◽  
Bzip Transcription Factor ◽  
General Strategy ◽  
Invasive Approach ◽  
Acid Supplementation ◽  
Regenerative Ability

AbstractAging is associated with reduced capacity for tissue repair, perhaps the most critical of which is a decline in the ability of aged neurons to recover after injury. Identifying factors that improve the regenerative ability of aging neurons is a prerequisite for therapy design and remains an enormous challenge, yet many of the genes that play a role in regeneration of youthful axons do not regulate axon regeneration in older animals2,9, highlighting the need to identify aging-specific regeneration mechanisms. Previously, we found that increased DAF-16/FOXO activity enhances the regenerative ability of mechanosensory axons in aged animals9. Here we show that DAF-16/FOXO mediates its pro-regenerative effects by upregulating folate metabolism genes via the ZIP-5 bZIP transcription factor. Remarkably, dietary folic acid supplementation improves the regeneration of aging C. elegans axons. Enzymes regulating folate metabolism are also up-regulated in regenerating zebrafish fins, and we show that dietary folic acid supplementation post-amputation enhances fin regrowth in aging zebrafish. Our results demonstrate that boosting folate metabolism is a conserved and non-invasive approach to increase the regenerative capacity of aging neurons and tissues. Given that lower folate status has been linked with reduced cognition in the elderly17, maintaining optimal folate metabolism may be a general strategy to achieve healthy brain aging.

scholarly journals Folate Supplementation during Oocyte Maturation Positively Impacts the Folate-Methionine Metabolism in Pre-Implantation Embryos

2021 ◽  
Author(s):  
Sikander Saini ◽  
Vishal Sharma ◽  
Shama Ansari ◽  
Amit Kumar ◽  
Abhishek Thakur ◽  
...  
Keyword(s):  
Folic Acid ◽  
Production Rate ◽  
Oocyte Maturation ◽  
Folic Acid Supplementation ◽  
Folate Metabolism ◽  
Acid Supplementation ◽  
Maturation Medium ◽  
Metabolism Enzymes ◽  
Methionine Cycle ◽  
Folate Transporters

Abstract Folic acid is vital for DNA synthesis and methylations through one-carbon (C1) metabolism. Thus, it is essential for cell division during embryonic development. The present study investigated the effect of folic acid supplementation on oocyte maturation, blastocyst development and the expression of folate transporters as well as folate metabolism enzymes in oocytes and pre-implantation embryos of goat. Immature goat oocytes, matured in maturation medium comprising different folic acid concentrations (0, 10, 50, 100 and 150 µM), were in vitro fertilized and cultured. Cumulus expansion markers (Ptx3 and Ptgs2) in cumulus cells were highly upregulated after 50 µM folic acid supplementation indicating higher degree of maturation. Supplementation of 50 µM folic acid during oocyte maturation resulted in significantly higher blastocyst production rate, reduction in intracellular ROS levels as well as upregulation of the transcripts for folate transporters and key folate-methionine cycle enzymes in comparison to control. The present study demonstrates the existence of active folate-methionine cycle in oocytes and pre-implantation goat embryos. Supplementation of 50 µM folic acid in maturation medium increases the blastocyst production rate, improves oocyte maturation, reduces ROS production as well as upregulate the expression of Folr1 and folate metabolism enzyme, Mtr.

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