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Journal of Assisted Reproduction and Genetics

25-09-2024 | Reproductive physiology and disease

TET1 overexpression affects cell proliferation and apoptosis in aging ovaries

Authors: Qiang Feng, Qirong Li, Yurui Hu, Zhan Wang, Hengzong Zhou, Chao Lin, Dongxu Wang

Published in: Journal of Assisted Reproduction and Genetics

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Abstract

Purpose

Along with the progress of society, human life expectancy has been increasing, and late marriage and late childbearing are the current trend. Since reproductive aging affects fertility, ovarian aging in women has become a major reproductive health issue in the current society. During ovarian aging, DNA methylation levels may change. The ten-eleven translocation (TET) protein family proteins TET1, TET2, and TET3 are important DNA demethylation enzymes, and differential expression of TET1, TET2, and TET3 may affect the proliferation and apoptosis of aging ovarian cells. The aim of this study was to investigate the role of TET1 in the regulation of ovarian aging.

Methods

The expression of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) was analyzed by immunofluorescence (IF) in young and aging ovaries of six 6–8-week-old female mice and six 6–8-month-old female mice. Then, the expression pattern of the TET protein family in young and aging ovaries of mice was investigated. To determine the impact of TET1 on ovarian development, the aging of IOSE-80, KGN, and SKOV-3 cells was induced with D-galactosidase (D-gal). Cells were then transfected using the TET1 overexpression vector or si-TET1. We assessed the proliferation and apoptosis of aging cells after transfection and analyzed the regulatory effect of TET1 expression on aging cells. Additionally, we verified the Tet1 expression in Tet1-KO mice.

Results

The 5mC to 5hmC transition, oocyte maturation, and blastocyst rate were reduced in aging mice compared to young mice. In aging mice ovaries, the expression levels of Tet1, Tet2, and Tet3 were reduced significantly, with Tet1 being particularly pronounced. The overexpression of TET1 promoted proliferation and inhibited apoptosis in aging human ovarian cells. Furthermore, Tet1 expression was very low in Tet1-KO C57BL/6 J mice ovaries.

Conclusion

This study demonstrates that the expression levels of TET family proteins are low in aging ovaries, and the overexpression of TET1 can promote proliferation and inhibit apoptosis in aging ovarian cells.
Appendix
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Metadata
Title
TET1 overexpression affects cell proliferation and apoptosis in aging ovaries
Authors
Qiang Feng
Qirong Li
Yurui Hu
Zhan Wang
Hengzong Zhou
Chao Lin
Dongxu Wang
Publication date
25-09-2024
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-024-03271-x