Knockout of RNA Binding Protein MSI2 Impairs Follicle Development in the Mouse Ovary: Characterization of MSI1and MSI2 during Folliculogenesis

Biomolecules

Nicole A. Siddall¹  Gary R. Hime¹  Thomas Graf²  Luisa I. De Andres²  Janet E. Holt³  Evan Boon³  Alexander P. Sobinoff⁴  Eileen A. McLaughlin⁴  Kara M. Gunter⁴  Barbara A. Fraser⁴  Jessie M. Sutherland⁴  Victoria Pye⁴  Ilana R. Bernstein⁴ 

[1] Anatomy and Neuroscience, University of Melbourne, Parkville VIC 3010, Australia;Differentiation and Cancer Program, Center for Genomic Regulation and UPF, Barcelona 08000, Spain;School of Biomedical Sciences & Pharmacy, University of Newcastle, Callaghan NSW 2308, Australia;School of Environmental and Life Sciences, University of Newcastle, Callaghan NSW 2308, Australia;

关键词: fertility;    Musashi;    oocyte;    granulosa cell;    oogenesis;   

DOI  :  10.3390/biom5031228

来源: DOAJ

【 摘 要 】

Characterizing the mechanisms underlying follicle development in the ovary is crucial to understanding female fertility and is an area of increasing research interest. The RNA binding protein Musashi is essential for post-transcriptional regulation of oocyte maturation in Xenopus and is expressed during ovarian development in Drosophila. In mammals Musashi is important for spermatogenesis and male fertility, but its role in the ovary has yet to be characterized. In this study we determined the expression of mammalian Musashi proteins MSI1 and MSI2 during mouse folliculogenesis, and through the use of a MSI2-specific knockout mouse model we identified that MSI2 is essential for normal follicle development. Time-course characterization of MSI1 and MSI2 revealed distinct differences in steady-state mRNA levels and protein expression/localization at important developmental time-points during folliculogenesis. Using a gene-trap mouse model that inactivates Msi2, we observed a significant decrease in ovarian mass, and change in follicle-stage composition due to developmental blocking of antral stage follicles and pre-antral follicle loss through atresia. We also confirmed that hormonally stimulated Msi2-deficient mice produce significantly fewer MII oocytes (60.9% less than controls, p < 0.05). Furthermore, the majority of these oocytes are of poor viability (62.2% non-viable/apoptotic, p < 0.05), which causes a reduction in female fertility evidenced by decreased litter size in Msi2-deficient animals (33.1% reduction to controls, p < 0.05). Our findings indicate that MSI1 and MSI2 display distinct expression profiles during mammalian folliculogenesis and that MSI2 is required for pre-antral follicle development.

【 授权许可】

Unknown