Jeon Hyuk-Joon, Kang Minsung, Kim Jae-Sung, Oh Jeong Su
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Korea.
Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
J Cell Physiol. 2022 Jan;237(1):833-845. doi: 10.1002/jcp.30557. Epub 2021 Aug 18.
A prolonged time span between ovulation and fertilization can cause postovulatory aging of oocytes, which impairs oocyte quality and subsequent embryo development. Telomere attrition has long been considered as the primary hallmark of aging or the cause of age-associated diseases. However, the status of telomere and its regulation during postovulatory oocyte aging are poorly understood. Here we found that oocytes experience telomere shortening during postovulatory aging, although they have the capacity to maintain telomere length. However, translationally controlled tumor protein (TCTP) overexpression could reverse age-associated telomere shortening by upregulating telomerase activity in mouse oocytes. Telomere length in mature oocytes gradually decreased with postovulatory aging, which was associated with a marked reduction in TRF1 expression, decreased telomerase activity, and decreased homologous combination (HR)-based alternative lengthening of telomeres (ALT) with a concomitant increase in oxidative stress. Surprisingly, however, overexpression of TCTP led to a remarkable increase in telomere length during postovulatory aging. Notably, neither TRF1 nor BRCA1 level was altered by TCTP overexpression. Moreover, TCTP-mediated telomere lengthening was not blocked by HR inhibition. In striking contrast, telomerase activity, as well as TERT and TERC levels, increased after TCTP overexpression. Importantly, unlike the chromosome-wide distribution of endogenous TCTP, overexpressed TCTP was ectopically localized at telomeres, implying that TCTP overexpression is required to increase telomerase activity. Collectively, our results demonstrate that TCTP prevents telomere attrition during postovulatory aging by upregulating telomerase activity in mouse oocytes.
排卵与受精之间的时间间隔延长会导致卵母细胞排卵后老化，这会损害卵母细胞质量及随后的胚胎发育。端粒磨损长期以来一直被认为是衰老的主要标志或与年龄相关疾病的病因。然而，排卵后卵母细胞老化过程中端粒的状态及其调控机制却鲜为人知。在此，我们发现卵母细胞在排卵后老化过程中会经历端粒缩短，尽管它们有维持端粒长度的能力。然而，翻译控制肿瘤蛋白（TCTP）的过表达可通过上调小鼠卵母细胞中的端粒酶活性来逆转与年龄相关的端粒缩短。成熟卵母细胞的端粒长度随着排卵后老化而逐渐缩短，这与TRF1表达显著降低、端粒酶活性下降、基于同源重组（HR）的端粒替代延长（ALT）减少以及氧化应激增加有关。然而，令人惊讶的是，TCTP的过表达导致排卵后老化过程中端粒长度显著增加。值得注意的是，TCTP过表达并未改变TRF1或BRCA1的水平。此外，TCTP介导的端粒延长未被HR抑制所阻断。与之形成鲜明对比的是，TCTP过表达后端粒酶活性以及TERT和TERC水平均增加。重要的是，与内源性TCTP在全染色体上的分布不同，过表达的TCTP异位定位于端粒，这意味着需要TCTP过表达来增加端粒酶活性。总体而言，我们的结果表明，TCTP通过上调小鼠卵母细胞中的端粒酶活性来防止排卵后老化过程中的端粒磨损。
