Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1228-1244 |
| Number of pages | 17 |
| Journal | Biomolecules |
| Volume | 5 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 7 Jul 2015 |
| Externally published | Yes |
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Knockout of rna binding protein msi2 impairs follicle development in the mouse ovary : Characterization of msi1 and msi2 during folliculogenesis. / Sutherland, Jessie M.; Sobinoff, Alexander P.; Gunter, Kara M.; Fraser, Barbara A.; Pye, Victoria; Bernstein, Ilana R.; Boon, Evan; Siddall, Nicole A.; De Andres, Luisa I.; Hime, Gary R.; Holt, Janet E.; Graf, Thomas; McLaughlin, Eileen A.
In: Biomolecules, Vol. 5, No. 3, 07.07.2015, p. 1228-1244.Research output: Contribution to journal › Article
TY - JOUR
T1 - Knockout of rna binding protein msi2 impairs follicle development in the mouse ovary
T2 - Characterization of msi1 and msi2 during folliculogenesis
AU - Sutherland, Jessie M.
AU - Sobinoff, Alexander P.
AU - Gunter, Kara M.
AU - Fraser, Barbara A.
AU - Pye, Victoria
AU - Bernstein, Ilana R.
AU - Boon, Evan
AU - Siddall, Nicole A.
AU - De Andres, Luisa I.
AU - Hime, Gary R.
AU - Holt, Janet E.
AU - Graf, Thomas
AU - McLaughlin, Eileen A.
PY - 2015/7/7
Y1 - 2015/7/7
N2 - 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.
AB - 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.
KW - Fertility
KW - Granulosa cell
KW - Musashi
KW - Oocyte
KW - Oogenesis
KW - RNA-Binding Proteins/genetics
KW - Gene Knockout Techniques
KW - Ovarian Follicle/growth & development
KW - Animals
KW - Gene Expression Regulation, Developmental
KW - Female
KW - Mice
KW - Nerve Tissue Proteins/deficiency
UR - http://www.scopus.com/inward/record.url?scp=85012059533&partnerID=8YFLogxK
UR - http://www.mendeley.com/research/knockout-rna-binding-protein-msi2-impairs-follicle-development-mouse-ovary-characterization-msi1-msi-1
U2 - 10.3390/biom5031228
DO - 10.3390/biom5031228
M3 - Article
VL - 5
SP - 1228
EP - 1244
JO - Biomolecules
JF - Biomolecules
SN - 2218-273X
IS - 3
ER -