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

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.

Metabolic enhancement of the one carbon metabolism (OCM) in bovine oocytes IVM increases the blastocyst rate: evidences for a OCM checkpoint

“…Previous attempts to provide such a support had focused on the supplementation of single metabolic enhancers 19 , 20 and resulted in increased blastocyst rate. Our support appeared more effective as resulting in a 107% increase of the blastocyst rate, which may depend on the use of multiple enhancers and/or on a putative higher sensitivity of the bovine species to folates.…”

İnferti̇l Hastalarin Granüloza Hücreleri̇nde Li̇qui̇ri̇ti̇geni̇n’i̇n Lösemi̇ İnhi̇bi̇tör Faktör Reseptörü Üzeri̇ne Etki̇leri̇

“…Bütün bunlara bağlı olarak ovaryen bozukluklar ve infertilite ortaya çıkar. Antioksidanların, diğer moleküllerin oksidasyonunu yavaşlatabildiği veya önleyebildiği ve hücresel hasara neden olabilecek serbest radikallerin üretimini azaltma potansiyeli taşıdığı düşünülmektedir (30)(31)(32)(33)(34).…”

“…Saini ve ark. da keçi embriyolarında eksternal folik asit takviyesinin oosit ve kümülüs hücre olgunlaşmasını, blastosist gelişimini ve folat taşıyıcılarının ekspresyonu arttırdığını ve ROS üretini azaltığını göstermişlerdir (34). Çeşitli çalışmalarda da melatoninin 'in embriyo üretimini desteklemek için olgunlaşma ortamına verilen oosit üzerindeki etkisini çalışmışlardır.…”