Development of specific DNA methylation patterns is required for normal spermatogenesis. DNA methyltransferases (DNMTs) use S-adenosylmethionine (SAM) produced in a pathway requiring 5,10-methylenetetrahydrofolate reductase (MTHFR). This thesis describes: testicular phenotype differences derived from Mthfr-deficiency in different mouse strains; the cellular Mthfr expression pattern during male germ cell development; and finally, changes to the DNA methylation of Mthfr-deficient sperm. Mthfr-deficient BALB/c, but not C57BL/6, mice have reduced neonatal germ cell proliferation but both have abnormal germ cells as adults. Germ cell MTHFR expression differed developmentally in parallel with DNMTs associated with de novo methylation. Sperm from mice with reduced Mthfr levels or dietary folate deficiency had differential DNA methylation at multiple loci, compared to wildtype mice, indicating that maintenance as well as acquisition of methylation can be altered by SAM-reduction. These results highlight the important role of folate in sperm development throughout life.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.116083 |
| Date | January 2008 |
| Creators | Cushnie, Duncan Wells. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Human Genetics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002826226, proquestno: AAIMR67024, Theses scanned by UMI/ProQuest. |
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