Loss of oocyte Rps26 in mice arrests oocyte growth and causes premature ovarian failure.
Loss of oocyte Rps26 in mice arrests oocyte growth and causes premature ovarian failure.
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小鼠卵母细胞 Rps26 缺失会抑制卵母细胞生长并导致卵巢早衰
DOI：
10.1038/s41419-018-1196-3
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发表时间：
2018-11-19
影响因子：
9
通讯作者：
Chen ZJ
中科院分区：
文献类型：
--
作者：
Liu XM;Yan MQ;Ji SY;Sha QQ;Huang T;Zhao H;Liu HB;Fan HY;Chen ZJ
总体转录活性随着卵母细胞的生长而增加，并且在完全生长的卵母细胞中沉默。因此，在卵母细胞的生长过程中，染色质的构型发生了变化，但调控这些变化的分子机制仍有待阐明。在这里，我们研究了多囊卵巢综合征（PCOS）的易感基因，RPS 26，这是一个核糖体蛋白编码基因，在卵巢中高度表达，但其功能尚不清楚。Rps 26基因敲除小鼠卵母细胞后，卵泡从腔前卵泡发育为腔卵泡的过程受到抑制，而卵母细胞的染色质构型则停滞在非包围型核仁（NSN）向包围型核仁（SN）的转变。结果，所有卵母细胞在出生后第84天死亡，导致卵巢早衰（POF）。Rps 26的缺失导致mRNA转录水平降低，组蛋白H3 K4/H3 K9三甲基化和DNA 5-胞嘧啶甲基化水平降低，而这些是卵母细胞从NSN型向SN型转化所必需的。卵母细胞衍生的生长分化因子9、骨形态发生蛋白15和卵母细胞-颗粒细胞间隙连接蛋白37的低蛋白水平抑制卵母细胞生长并延缓卵泡发育。磷酸肌醇3-激酶/蛋白激酶B/叉头盒O-3a途径的破坏导致卵母细胞死亡和卵泡闭锁。这些结果为POF的临床诊断，特别是未经治疗的PCOS患者提供了遗传学线索。
Global transcriptional activity increases as oocytes grow and is silenced in fully grown oocytes. Thus, the chromatin configuration varies during oocyte growth, but the molecular mechanisms regulating these changes remain to be clarified. Here, we studied a susceptibility gene of polycystic ovary syndrome (PCOS),RPS26, which is a ribosomal protein-encoding gene that is highly expressed in the ovary, but the functions of which remain unknown. Specific knockout ofRps26in mouse oocytes resulted in retarded follicle development from pre-antral follicles to antral follicles, while the chromatin configurations of the oocytes were arrested at the transition from the non-surrounded nucleolus (NSN) to surrounded nucleolus (SN)-type. As a consequence, all oocytes died by postnatal day 84 resulting in premature ovarian failure (POF). Loss ofRps26in oocytes led to decreased mRNA transcription and low levels of histone trimethylation on H3K4/H3K9 and DNA methylation at 5-cytosine, high levels of which are required for oocytes to transform from NSN to SN-type. Low protein levels of oocyte-derived growth differentiation factor 9, bone morphogenetic protein 15, and the oocyte-granulosa cell gap junction protein connexin 37 inhibited oocyte growth and retarded follicle development. The disruption of the phosphoinositide 3-kinase/protein kinase B/Forkhead box O-3a pathway contributed to oocyte death and follicle atresia. These results provide genetic clues for the clinical diagnosis of POF, especially in PCOS patients without treatment.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1126/science.1171396
发表时间：
2009-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fan HY;Liu Z;Shimada M;Sterneck E;Johnson PF;Hedrick SM;Richards JS
通讯作者：
Richards JS
DOI：
10.1073/pnas.180295197
发表时间：
2000-08-29
影响因子：
11.1
作者：
Elvin, JA;Yan, CN;Matzuk, MM
通讯作者：
Matzuk, MM
影响因子：
56.9
作者：
Nakayam, J;Rice, JC;Grewal, SIS
通讯作者：
Grewal, SIS
影响因子：
3.8
作者：
Kageyama, Shun-ichiro;Liu, Honglin;Aoki, Fugaku
通讯作者：
Aoki, Fugaku