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多囊卵巢综合征患者颗粒细胞中ADAMTS1的表达水平与颗粒细胞功能、卵母细胞质量及胚胎发育相关。

Expression Level of ADAMTS1 in Granulosa Cells of PCOS Patients Is Related to Granulosa Cell Function, Oocyte Quality, and Embryo Development.

作者信息

Yang Guang, Yao Guidong, Xu Ziwen, Fan Huiying, Liu Xingui, He Jiahuan, Kong Yue, Kong Deqi, Bai Yucheng, He Qina, Zhang Tongwei, Zhang Junya, Sun Yingpu

机构信息

Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Cell Dev Biol. 2021 Apr 12;9:647522. doi: 10.3389/fcell.2021.647522. eCollection 2021.

Abstract

A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) is an extracellular matrix metalloproteinase that plays an important role in the process of ovulation. According to previous studies, the expression level of ADAMTS1 in the granulosa cells of polycystic ovarian syndrome (PCOS) patients and the mechanism for regulating oocyte quality and embryonic development potential are still unclear. Our research clarified that ADAMTS1 was significantly increased in granulosa cells of PCOS patients as compared to ovulatory controls. After silencing ADAMTS1 in granulosa cells, cell proliferation and E secretion were significantly inhibited, which may be related to the down-regulation of B-cell lymphoma 2 (Bcl2) family genes and key genes involved in E synthesis. Through retrospective analysis of the clinical data, it was found that the expression level of ADAMTS1 was significantly positively correlated to the oocyte maturation rate and good-quality embryo rate in PCOS patients. The downregulation of ADAMTS1 in primary granulosa cells lead to the changes in the expression of marker genes for oocyte and embryonic quality. By using immunofluorescence staining, it was found ADAMTS1 was expressed in various stages of pre-implantation embryo but its expression level gradually decreases with the development of the embryo. In addition, the silence of ADAMTS1 in 3PN zygotes significantly prolonged the development time of the zygote to the morula stage. This is, to our knowledge, the first time to explored the mechanism by which ADAMST1 is involved in affecting the quality of oocytes and embryonic development potential, which will provide new evidence for further understanding of the follicular microenvironment and embryo development.

摘要

含血小板反应蛋白基序的解聚素和金属蛋白酶1(ADAMTS1)是一种细胞外基质金属蛋白酶,在排卵过程中起重要作用。根据以往研究,多囊卵巢综合征(PCOS)患者颗粒细胞中ADAMTS1的表达水平以及调节卵母细胞质量和胚胎发育潜能的机制仍不清楚。我们的研究表明,与排卵对照组相比,PCOS患者颗粒细胞中ADAMTS1显著增加。在颗粒细胞中沉默ADAMTS1后,细胞增殖和E分泌受到显著抑制,这可能与B细胞淋巴瘤2(Bcl2)家族基因和参与E合成的关键基因的下调有关。通过对临床数据的回顾性分析,发现PCOS患者中ADAMTS1的表达水平与卵母细胞成熟率和优质胚胎率显著正相关。原代颗粒细胞中ADAMTS1的下调导致卵母细胞和胚胎质量标记基因表达的变化。通过免疫荧光染色发现,ADAMTS1在植入前胚胎的各个阶段均有表达,但其表达水平随着胚胎发育逐渐降低。此外,在三原核受精卵中沉默ADAMTS1显著延长了受精卵发育至桑椹胚阶段的时间。据我们所知,这是首次探索ADAMST1影响卵母细胞质量和胚胎发育潜能的机制,这将为进一步了解卵泡微环境和胚胎发育提供新的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7b8/8075003/44dad99baa53/fcell-09-647522-g001.jpg

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