Department of Veterinary Medicine, Konkuk University, Seoul, Republic of Korea.
Korean Institute of Oriental Medicine, Daejeon, Republic of Korea.
Cell Prolif. 2022 Oct;55(10):e13288. doi: 10.1111/cpr.13288. Epub 2022 Jun 29.
As a component of Endosomal Sorting Complex Required for Transport (ESCRT) complex I, the tumor susceptibility gene 101 (Tsg101) carries out multiple functions. In this work, we report that oocyte-specific deletion of tumor susceptibility gene 101 (Tsg101) leads to age-dependent oocyte demise in mice.
Tsg101 floxed mice (Tsg101 ) were bred with Zp3 transgenic mice to examine oocyte-specific roles of Tsg101. Multiple cellular and molecular biological approaches were taken to examine what leads to oocyte demise in the absence of Tsg101.
The death of oocytes from Zp3 /Tsg101 (Tsg101 thereafter) mice showed a strong correlation with sexual maturation, as gonadotropin-releasing hormone antagonist injections improved the survival rate of oocytes from 5-week-old Tsg101 mice. Maturation of oocytes from prepubertal Tsg101 mice proceeded normally, but was largely abnormal in oocytes from peripubertal Tsg101 mice, showing shrinkage or rupture. Endolysosomal structures in oocytes from peripubertal Tsg101 mice showed abnormalities, with aberrant patterns of early and late endosomal markers and a high accumulation of lysosomes. Dying oocytes showed plasma membrane blebs and leakage. Blockage of endocytosis in oocytes at 4°C prevented cytoplasmic shrinkage of oocytes from Tsg101 mice until 9 h. The depletion of tsg-101 in Caenorhabditis elegans increased the permeability of oocytes and embryos, suggesting a conserved role of Tsg101 in maintaining membrane integrity.
Collectively, Tsg101 plays a dual role in maintaining the integrity of membranous structures, which is influenced by age in mouse oocytes.
作为内体分选复合物所需运输（ESCRT）复合物 I 的一个组成部分，肿瘤易感性基因 101（Tsg101）具有多种功能。在这项工作中，我们报道了卵母细胞特异性缺失肿瘤易感性基因 101（Tsg101）会导致小鼠卵母细胞的年龄依赖性死亡。
Tsg101 基因敲入（Tsg101）小鼠与 Zp3 转基因小鼠交配，以研究 Tsg101 对卵母细胞的特异性作用。采用多种细胞和分子生物学方法来研究在没有 Tsg101 的情况下导致卵母细胞死亡的原因。
Zp3/Tsg101（此后称为 Tsg101）小鼠的卵母细胞死亡与性成熟密切相关，因为促性腺激素释放激素拮抗剂注射可提高 5 周龄 Tsg101 小鼠卵母细胞的存活率。来自青春期前 Tsg101 小鼠的卵母细胞成熟过程正常，但来自青春期 Tsg101 小鼠的卵母细胞大部分异常，显示出缩小或破裂。来自青春期前 Tsg101 小鼠的卵母细胞中的内溶酶体结构异常，早期和晚期内体标记物的模式异常，溶酶体大量积累。死亡的卵母细胞显示出质膜泡和渗漏。在 4°C 下阻断卵母细胞的内吞作用可防止 Tsg101 小鼠卵母细胞的细胞质收缩，直到 9 小时。在秀丽隐杆线虫中耗尽 tsg-101 增加了卵母细胞和胚胎的通透性，这表明 Tsg101 在维持膜完整性方面具有保守作用。
总的来说，Tsg101 在维持膜状结构的完整性方面发挥双重作用，这在小鼠卵母细胞中受年龄的影响。
