Oocyte aging is controlled by mitogen-activated protein kinase signaling.
Oocyte aging is controlled by mitogen-activated protein kinase signaling.
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卵母细胞的衰老是由丝裂原活化蛋白激酶信号控制的。
DOI：
10.1111/acel.13386
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发表时间：
2021-06
期刊：
影响因子：
7.8
通讯作者：
Tzur YB
中科院分区：
文献类型：
--
作者：
Achache H;Falk R;Lerner N;Beatus T;Tzur YB
卵子发生是衰老过程中最先失败的过程之一。在女性中，大多数卵母细胞在生命的第四个十年中已经不能成功完成减数分裂。对秀丽隐杆线虫的研究揭示了控制寿命的保守遗传途径，但我们对蠕虫和人类生殖衰老的了解有限。具体来说，很少有人知道生殖细胞的内部信号，决定了卵原生物钟。在这里，我们报告了一个彻底的特点，在蠕虫生殖细胞老化过程中的变化。我们发现，排卵停止后不久，生殖细胞增殖下降，而凋亡继续，导致生殖细胞数量逐渐减少。在衰老后期，我们观察到减数分裂进程受到干扰，交换指定和DNA双链断裂修复减少。此外，我们检测到老化过程中成熟卵母细胞的质量下降，这反映在尺寸减小和同源物间距离延长，这也是在人类卵母细胞中观察到的表型。许多这些改变的过程以前归因于幼蠕虫中MAPK信号的变化。为了支持这一点，我们观察到MPK-1在老化过程中的激活动力学变化。因此，我们测试的假设，MAPK控制卵母细胞的质量在老年蠕虫使用遗传和药理学工具。我们发现，在具有高水平活化MPK-1的突变体中，卵母细胞质量比野生型蠕虫更快地恶化，而MPK-1水平的降低提高了质量。因此，我们的数据表明，MAPK信号控制生殖细胞老化，并可用于减轻卵子发生质量下降的速度。In C.在线虫生殖系中，衰老导致几种变化，包括交叉指定、凋亡和成熟卵母细胞的质量。所有这些都是以前被证明是由MAPK信号控制。我们发现，当MAPK过度激活时，停滞卵母细胞的质量较低，但可以通过遗传或药理学工具降低MAPK来改善。
Oogenesis is one of the first processes to fail during aging. In women, most oocytes cannot successfully complete meiotic divisions already during the fourth decade of life. Studies of the nematode Caenorhabditis elegans have uncovered conserved genetic pathways that control lifespan, but our knowledge regarding reproductive aging in worms and humans is limited. Specifically, little is known about germline internal signals that dictate the oogonial biological clock. Here, we report a thorough characterization of the changes in the worm germline during aging. We found that shortly after ovulation halts, germline proliferation declines, while apoptosis continues, leading to a gradual reduction in germ cell numbers. In late aging stages, we observed that meiotic progression is disturbed and crossover designation and DNA double‐strand break repair decrease. In addition, we detected a decline in the quality of mature oocytes during aging, as reflected by decreasing size and elongation of interhomolog distance, a phenotype also observed in human oocytes. Many of these altered processes were previously attributed to MAPK signaling variations in young worms. In support of this, we observed changes in activation dynamics of MPK‐1 during aging. We therefore tested the hypothesis that MAPK controls oocyte quality in aged worms using both genetic and pharmacological tools. We found that in mutants with high levels of activated MPK‐1, oocyte quality deteriorates more rapidly than in wild‐type worms, whereas reduction of MPK‐1 levels enhances quality. Thus, our data suggest that MAPK signaling controls germline aging and could be used to attenuate the rate of oogenesis quality decline. In C. elegans germline, aging leads to several changes, including crossover designation, apoptosis, and the quality of the mature oocytes. All of these were previously shown to be controlled by MAPK signaling. We show that arrested oocyte's quality is lower when MAPK is overactivated, yet it can be improved by lowering MAPK via genetic or pharmacological tools.
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DOI：
10.4161/worm.21146
发表时间：
2013-01-01
期刊：
Worm
影响因子：
--
作者：
Chasnov JR
通讯作者：
Chasnov JR
影响因子：
11.8
作者：
Arur, Swathi;Ohmachi, Mitsue;Berkseth, Matt;Nayak, Sudhir;Hansen, David;Zarkower, David;Schedl, Tim
通讯作者：
Schedl, Tim
DOI：
10.18632/aging.100040
发表时间：
2009-04-20
期刊：
Aging
影响因子：
--
作者：
Blagosklonny MV;Hall MN
通讯作者：
Hall MN
影响因子：
11.8
作者：
Colaiácovo, MP;MacQueen, AJ;Villeneuve, AM
通讯作者：
Villeneuve, AM
影响因子：
3.3
作者：
Bohr, Tisha;Ashley, Guinevere;Bhalla, Needhi
通讯作者：
Bhalla, Needhi