Increased number of multi-oocyte follicles (MOFs) in juvenile p27Kip1 mutant mice: Potential role of granulosa cells Journal Article
| Authors: | Pérez-Sanz, J.; Arluzea, J.; Matorras, R.; Gonzalez-Santiago, N.; Bilbao, J.; Yeh, N.; Barlas, A.; Romin, Y.; Manova-Todorova, K.; Koff, A.; De La Hoz, C. |
| Article Title: | Increased number of multi-oocyte follicles (MOFs) in juvenile p27Kip1 mutant mice: Potential role of granulosa cells |
| Abstract: | STUDY QUESTION: Why are female mice that lack a functional p27 protein infertile?SUMMARY ANSWERThe absence of a functional p27 leads to a dramatic increase in the number of multi-oocyte follicles (MOFs) in juvenile female mice; p27 would promote the individualization of follicles favoring the development of fertile eggs.WHAT IS KNOWN ALREADYp27-/- female mice are infertile. p27 suppresses excessive follicular endowment and activation and promotes follicular atresia in mice.MATERIALS AND METHODSOvaries from wild type (WT) and p27Kip1 mutant mice aged 2, 4 and 12 weeks were subjected to immunohistochemistry/ immunofluorescence. The slides with whole organs serially sectioned were scanned and examined by image analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with WT, p27Kip1 mutant pre-pubertal mice had a greater number of oocytes, a greater number of growing follicles and a greater number of MOFs. These differences were statistically significant (P < 0.05), particularly in the case of MOFs (P > 0.001). The unusually large number of MOFs in juvenile p27-deficient mice is a novel observation. In WT mice p27 protein remains present in the oocyte nucleus but gradually decreases in the ooplasm during follicular growth, while granulosa cells show dynamic, follicle stage-related changes. LIMITATIONS, REASONS FOR CAUTION: These results have been obtained in mice and they cannot be directly extrapolated to humans. WIDER IMPLICATIONS OF THE FINDINGS: The dramatic increase in the numbers of MOFs in juvenile p27 mutants has not been previously reported. The number of MOFs declines sharply as the mice become sexually mature, pointing to their negative selection. These findings open a new approach to the study of sterility.STUDY FUNDING/COMPETING INTERESTSThis study has been funded by the Basque Government, Dept. of Health grant 2007111063 and Dept. of Industry (Saiotek) grant S-PC11UN008. Jairo Perez-Sanz was the recipient of a grant from Fundación Jesús de Gangoiti Barrera. The authors have no conflicts of interest to declare. © 2013 The Author. |
| Keywords: | immunohistochemistry; controlled study; protein expression; mutation; nonhuman; comparative study; protein localization; cell proliferation; animal cell; mouse; oocyte; animals; mice; animal tissue; mus; cell growth; image analysis; embryo; animal experiment; cell differentiation; immunofluorescence; infertility; ovary; statistical significance; cyclin dependent kinase inhibitor 1b; cyclin-dependent kinase inhibitor p27; cell nucleus; ovarian follicle; female infertility; ovary development; sexual maturation; p27kip1; follicular phase; ovary follicle development; ovary function; female sterility; granulosa cell; granulosa cells; prepuberty; follicle; granulosa; mof; multioocyte follicle; ovary follicle atresia; ovary follicle cell |
| Journal Title: | Human Reproduction |
| Volume: | 28 |
| Issue: | 4 |
| ISSN: | 0268-1161 |
| Publisher: | Oxford University Press |
| Date Published: | 2013-04-01 |
| Start Page: | 1023 |
| End Page: | 1030 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 23300200 |
| DOI: | 10.1093/humrep/des436 |
| PMCID: | PMC4439520 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2013" - "CODEN: HUREE" - ":doi 10.1093/humrep/des436" - "Source: Scopus" |
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32Romin
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