Tet1 Deficiency Leads to Premature Reproductive Aging by Reducing Spermatogonia Stem Cells and Germ Cell Differentiation.

ABSTRACT: Ten-eleven translocation (Tet) enzymes are involved in DNA demethylation, important in regulating embryo development, stem cell pluripotency and tumorigenesis. Alterations of DNA methylation with age have been shown in various somatic cell types. We investigated whether Tet1 and Tet2 regulate aging. We showed that Tet1-deficient mice undergo a progressive reduction of spermatogonia stem cells and spermatogenesis and thus accelerated infertility with age. Tet1 deficiency decreases 5hmC levels in spermatogonia and downregulates a subset of genes important for cell cycle, germ cell differentiation, meiosis and reproduction, such as Ccna1 and Spo11, resulting in premature reproductive aging. Moreover, Tet1 and 5hmC both regulate signaling pathways key for stem cell development, including Wnt a

SUBMITTER: Huang G 

PROVIDER: S-EPMC7049665 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature