Loss-of-function of sox3 causes follicle development retardation and reduces fecundity in zebrafish
Loss-of-function of sox3 causes follicle development retardation and reduces fecundity in zebrafish
复制标题
sox3 功能丧失导致斑马鱼卵泡发育迟缓并降低繁殖力
DOI：
10.1007/s13238-018-0603-y
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发表时间：
2019-05-01
期刊：
影响因子：
21.1
通讯作者：
Zhou, Rongjia
中科院分区：
文献类型：
--
作者：
Hong, Qiang;Li, Cong;Zhou, Rongjia
在脊椎动物中，卵泡发生是雌性配子产生所必需的。然而，卵泡发育的分子机制，特别是卵巢细胞凋亡的调控，仍然是一个谜。在这里，我们使用CRISPR/ Cas9产生了sox 3敲除斑马鱼系。sox 3基因敲除导致雌性卵泡发育迟缓和生育力降低。Sox 3（-/-）和野生型卵巢转录组的比较分析显示，Sox 3参与卵巢类固醇生成和凋亡的途径。sox 3基因敲除可促进卵泡凋亡，在sox 3（-/-）卵巢的III期和IV期卵泡体细胞中检测到明显的凋亡信号。此外，Sox 3可以结合并激活cyp 19 a1 a的启动子。Cyp 19 a1 a表达上调促进17 β-雌二醇的合成，从而抑制卵泡发育过程中的细胞凋亡。因此，Sox 3通过17 β-E2连接细胞凋亡抑制，作为Cyp 19 a1 a表达的调节剂发挥作用，这与改善雌性生殖力有关。
Folliculogenesis is essential for production of female gametes in vertebrates. However, the molecular mechanisms underlying follicle development, particularly apoptosis regulation in ovary, remain elusive. Here, we generated sox3 knockout zebrafish lines using CRISPR/ Cas9. sox3 knockout led to follicle development retardation and a reduced fecundity in females. Comparative analysis of transcriptome between sox3(-/-) and wild-type ovaries revealed that Sox3 was involved in pathways of ovarian steroidogenesis and apoptosis. Knockout of sox3 promoted follicle apoptosis and obvious apoptosis signals were detected in somatic cells of stages III and IV follicles of sox3(-/-) ovaries. Moreover, Sox3 can bind to and activate the promoter of cyp19a1a. Up-regulation of Cyp19a1a expression promoted 17 beta-estradiol synthesis, which inhibited apoptosis in follicle development. Thus, Sox3 functions as a regulator of Cyp19a1a expression, via 17 beta-E2 linking apoptosis suppression, which is implicated in improving female fecundity.