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. Although the oocytes contain endogenous pool of folates for development, the present study investigated the effect of external 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 improves oocyte maturation, the blastocyst production rate, reduces ROS production as well as upregulate the expression of FOLR1 and folate metabolism enzyme, MTR.
Highlights
Folate is the group name commonly used for folic acid and its derivatives having similar activity
The effect of supplementation of maturation medium with different concentrations of folic acid was studied in cumulus cells by qRT-PCR using the cumulus expansion markers (Ptgs2 and Pentraxin 3 (Ptx3)) and Gapdh for normalization
GDF-9 secreted by the oocyte has been reported to act as a key factor in cumulus expansion [23], which improves oocyte developmental competence by regulating several crucial granulosa cell enzymes involved in cumulus cell expansion [24]
Summary
Folate is the group name commonly used for folic acid and its derivatives having similar activity. Consumption of high dose of folic acid during pregnancy was found to be associated with the decreased follicular development [5], delayed psychomotor development in newborn [6] and increased risk of asthma in the child [7]. The pups of mice kept on high folate diet showed altered expression of genes linked to neurodevelopment or autism spectrum disorder [8]. These findings support the need for optimization of the folic acid dose to improve the quality of oogenesis and to prevent the birth defects
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