Abstract
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 17β-estradiol synthesis, which inhibited apoptosis in follicle development. Thus, Sox3 functions as a regulator of Cyp19a1a expression, via 17β-E2 linking apoptosis suppression, which is implicated in improving female fecundity.
Highlights
In the vertebrate ovary, follicles are the functional units for oogenesis, which contain oocytes, granulosa cells and thecaQiang Hong and Cong Li are co-first authors.Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.cells
To characterize both sox3f7 and sox3f40 zebrafish at the molecular level, quantitative real-time PCR was performed, which revealed that sox3 was significantly reduced in sox3 knockout ovaries compared to wild type ovaries (Fig. S2), suggesting transcript destabilization and degradation of Sox3f7 and Sox3f40 in the mutants by nonsense-mediated mRNA decay (NMD) due to premature termination codons (Baker and Parker, 2004; Popp and Maquat, 2016)
We provided a molecular mechanism of apoptosis-regulated follicle development in zebrafish
Summary
Follicles are the functional units for oogenesis, which contain oocytes, granulosa cells and theca. The communication between oocytes and granulosa cells is essential for oocyte development (Eppig, 2001). The bidirectional communication between oocytes and somatic cells is important for oogenesis. Studies have shown that autophagy of ovarian somatic cells is involved in regulation of follicular development by maintaining cell homeostasis (Yuan et al, 2015), while apoptosis of granulosa cells is pivotal for follicular development through atresia of many early follicles to ensure growth and maturation of some dominant follicles (Matsuda et al, 2012). The molecular mechanisms connecting apoptosis in ovary to follicle development remain largely unknown. Identification of key regulators of apoptosis and relevant pathways is important for understanding ovarian functions
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