Loss-of-function of sox3 causes follicle development retardation and reduces fecundity in zebrafish

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. Electronic supplementary material The online version of this article (10.1007/s13238-018-0603-y) contains supplementary material, which is available to authorized users.

DNA methylation modification is associated with gonadal differentiation in Monopterus albus

“…Foxa1 can activate dnmt3aa transcription, which probably upregulates the methylation levels of key genes in gonad differentiation, including foxl2 and cyp19a1a . The Foxl2-Cyp19a1a pathway was essential for development and function maintenance of ovary [ 23 ]. To further explore association of DNA methylation with gonad development, we analyzed DNA methylation levels of the key genes in the synthesis pathway of female hormone estradiol-17β.…”

“…These results indicated the DNA methylation levels of 5′ flanking regions of both foxl2 and cyp19a1a were associated with their expression during gonadal differentiation. Both Foxl2 and Cyp19a1a promoted estrogen synthesis for ovary development [ 23 , 31 ] (Fig. 5 d).…”

“…Chromatin immunoprecipitation was performed according to our previous study [ 23 ]. Briefly, testis samples were minced with sterilized scissors in PBS and a final concentration of 1% formaldehyde-PBS was used for crosslinking for 20 min at room temperature.…”

Whole genome-wide chromosome fusion and new gene birth in the Monopterus albus genome

“…The syntenic Sox3 block from ancestral chromosome G is conserved, and Sox3 evolved into the male-determining gene Sry on the Y chromosome only in mammals [45,55], while Sox3 is essential for ovary development in zebrafish [56]. The syntenic Dmrt1 block retains from ancestral chromosome E in near all vertebrates, and Dmrt1 is a major factor for male development in mammals [57], birds [41], reptiles [58], amphibians [59] and fishes [60][61][62], regardless of its location on the Z/X/Y or autosomes.…”

RAB37 multiple alleles, transcription activation and evolution in mammals

“…Dual-luciferase reporter assays were performed according to our previous protocols [18]. Cells per 48-well were transfected with 0.5 μg recombinant construct and 10 ng pRL-TK (Cat# E2241, Promega) using LipofectamineTM 2000 (Cat# 11668027, Invitrogen).…”