Rescue of < i > bmp15 < /i > deficiency in zebrafish by mutation of < i > inha < /i > reveals mechanisms of BMP15 regulation of folliculogenesis

by Yue Zhai, Xin Zhang, Cheng Zhao, Ruijing Geng, Kun Wu, Mingzhe Yuan, Nana Ai, Wei Ge As an oocyte-specific growth factor, bone morphogenetic protein 15 (BMP15) plays a critical role in controlling folliculogenesis. However, the mechanism of BMP15 action remains elusive. Using zebrafish as the model, we created abmp15 mutant using CRISPR/Cas9 and demonstrated thatbmp15 deficiency caused a significant delay in follicle activation and puberty onset followed by a complete arrest of follicle development at previtellogenic (PV) stage without yolk accumulation. The mutant females eventually underwent female-to-male sex reversal to become functional males, which was accompanied by a series of changes in secondary sexual characteristics. Interestingly, the blockade of folliculogenesis and sex reversal inbmp15 mutant could be partially rescued by the loss of inhibin (inha-/-). The follicles of double mutant (bmp15-/-;inha-/-) could progress to mid-vitellogenic (MV) stage with yolk accumulation and the fish maintained their femaleness without sex reversal. Transcriptome analysis revealed up-regulation of pathways related to TGF- β signaling and endocytosis in the double mutant follicles. Interestingly, the expression of inhibin/activin βAa subunit (inhbaa) increased significantly in the double mutant ovary. Further knockout ofinhbaa in the triple mutant (bmp15-/-;inha-/-;inhbaa-/-) resulted in the loss of yolk granules again. The serum levels of estradiol (E2) and vitellogenin (Vt...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research