TET1 overexpression affects cell proliferation and apoptosis in aging ovaries.

IF 3.2 3区医学 Q2 GENETICS & HEREDITY

Journal of Assisted Reproduction and Genetics Pub Date : 2024-09-25 DOI:10.1007/s10815-024-03271-x

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

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引用次数: 0

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.

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TET1 过表达会影响衰老卵巢的细胞增殖和凋亡。

目的：随着社会的进步，人类的预期寿命不断延长，晚婚晚育成为当前的趋势。由于生殖衰老会影响生育能力，女性卵巢衰老已成为当今社会的一大生殖健康问题。在卵巢衰老过程中，DNA 甲基化水平可能会发生变化。十-十一转位（TET）蛋白家族蛋白TET1、TET2和TET3是重要的DNA去甲基化酶，TET1、TET2和TET3的不同表达可能会影响衰老卵巢细胞的增殖和凋亡。本研究旨在探讨TET1在卵巢衰老调控中的作用：方法：用免疫荧光法（IF）分析了6只6-8周龄雌性小鼠和6只6-8月龄雌性小鼠年轻卵巢和衰老卵巢中5-甲基胞嘧啶（5mC）和5-羟甲基胞嘧啶（5hmC）的表达。然后，研究了 TET 蛋白家族在小鼠年轻卵巢和衰老卵巢中的表达模式。为了确定TET1对卵巢发育的影响，用D-半乳糖苷酶（D-gal）诱导IOSE-80、KGN和SKOV-3细胞衰老。然后用 TET1 过表达载体或 si-TET1 转染细胞。我们评估了转染后衰老细胞的增殖和凋亡情况，并分析了 TET1 表达对衰老细胞的调控作用。此外，我们还验证了 Tet1-KO 小鼠中 Tet1 的表达情况：结果：与年轻小鼠相比，衰老小鼠的5mC向5hmC转变、卵母细胞成熟度和囊胚率都有所下降。在衰老小鼠卵巢中，Tet1、Tet2 和 Tet3 的表达水平显著降低，其中 Tet1 尤为明显。在衰老的人类卵巢细胞中，过表达 TET1 可促进细胞增殖，抑制细胞凋亡。此外，在 Tet1-KO C57BL/6 J 小鼠卵巢中，Tet1 的表达量非常低：本研究表明，TET 家族蛋白在衰老卵巢中的表达水平较低，而 TET1 的过表达可促进衰老卵巢细胞的增殖并抑制其凋亡。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Assisted Reproduction and Genetics 医学-妇产科学

CiteScore

5.70

自引率

9.70%

发文量

286

审稿时长

1 months

期刊介绍： The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species. The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.