Abstract Title:

Endogenous folates and single-carbon metabolism in the ovarian follicle, oocyte and pre-implantation embryo.

Abstract Source:

Reproduction. 2010 Jan 18. Epub 2010 Jan 18. PMID: 20083604

Abstract Author(s):

W Y Kwong, S J Adamiak, A Gwynn, R Singh, K D Sinclair


Maternal B-vitamin status at conception can affect fertility and the health of offspring. This study details transcript expression for genes encoding key enzymes in the linked methionine/folate cycles in the bovine/ovine oocyte, somatic cells of the ovarian follicle and pre-implantation embryo. Transcripts for all 12 enzymes studied and for the two folate receptors (FOLR1 and 2) and Reduced Folate Carrier (SCL19A1) were expressed in liver cells, but transcripts for Betaine-Homocysteine Methyltransferase and Methionine Adenosyl Transferase 1A were absent in all ovarian cells, and transcripts for FOLR2 was absent in embryonic cells. Transcripts for Glycine Methyltransferase were also absent in cumulus and granulosa cells. The absence of these enzymes could have a profound effect on single-carbon metabolism within the ovary and pre-implantation embryo. Immunocytochemical analysis revealed SCL19A1 protein expression on the plasma and basal-lateral membranes of the pre-implantation embryo. The folate antagonist methotrexate (MTX) enters the cell via SCL19A1 and, in the current study, MTX inclusion in culture media at either 1 or 10 microM from the 1-cell stage inhibited embryo development beyond the 8-cell stage. Hypoxanthine and thymidine (100 microM) increased the proportion of embryos that developed to blastocysts but cell number was reduced by 20%. The reduced uptake of [35S] methionine into intracellular S-adenosyl methionine and S-adenosyl homocysteine pools, together with reduced uptake of glutamate and tryptophan, were consistent with depleted intra-cellular pools of reduced folates. These data provide an insight into the importance of maternal dietary folate/B-vitamin status during the peri-conceptional period.

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