{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:51:06Z","timestamp":1790272266615,"version":"4.1.0"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Tet enzymes participate in DNA demethylation and play critical roles in stem cell pluripotency and differentiation. DNA methylation alters with age. We find that <jats:italic>Tet1<\/jats:italic> deficiency reduces fertility and leads to accelerated reproductive failure with age. Noticeably, <jats:italic>Tet1<\/jats:italic>-deficient mice at young age exhibit dramatically reduced follicle reserve and the follicle reserve further decreases with age, phenomenon consistent with premature ovarian failure (POF) syndrome. Consequently, <jats:italic>Tet1-<\/jats:italic>deficient mice become infertile by reproductive middle age, while age matched wild-type mice still robustly reproduce. Moreover, by single cell transcriptome analysis of oocytes, <jats:italic>Tet1<\/jats:italic> deficiency elevates organelle fission, associated with defects in ubiquitination and declined autophagy, and also upregulates signaling pathways for Alzheimer\u2019s diseases, but down-regulates X-chromosome linked genes, such as <jats:italic>Fmr1<\/jats:italic>, which is known to be implicated in POF. Additionally, <jats:italic>Line1<\/jats:italic> is aberrantly upregulated and endogenous retroviruses also are altered in <jats:italic>Tet1-<\/jats:italic>deficient oocytes. These molecular changes are consistent with oocyte senescence and follicle atresia and depletion found in premature ovarian failure or insufficiency. Our data suggest that <jats:italic>Tet1<\/jats:italic> enzyme plays roles in maintaining oocyte quality as well as oocyte number and follicle reserve and its deficiency can lead to POF.<\/jats:p>","DOI":"10.3389\/fcell.2021.644135","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T05:07:52Z","timestamp":1616476072000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["Tet1 Deficiency Leads to Premature Ovarian Failure"],"prefix":"10.3389","volume":"9","author":[{"given":"Linlin","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huasong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo_Liang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1097\/wad.0b013e31811ec130","article-title":"Fragile X premutation in a woman with cognitive impairment, tremor, and history of premature ovarian failure.","volume":"21","author":"Al-Hinti","year":"2007","journal-title":"Alzheimer Dis. 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