The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the mouse.
BACKGROUND
Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs).


METHODS
In this study we tested the expression of CDKIs p15, p16, p21 and p27 by immunohistochemistry to determine the role of CDKIs in the initiation of primordial follicle growth. Ovaries were collected from 60-day-old cycling B6D2F1/J mice (n = 16).


RESULTS
Expression of p15, p16, p21 and p27 did not vary in granulosa and theca cells by the follicle stage. However, p16 staining was stronger (++) in the oocytes of all primordial, and 57.4 +/- 3.1% of primary follicles compared to the remaining primary and more advanced follicles (+). Interestingly, primary follicles with weaker (+) oocyte staining for p16 had significantly larger mean follicle diameter compared to the primary and primordial follicles with stronger (++) oocyte staining (55.6 +/- 2.1 vs. 32.0 +/- 1.0 and 26.5 +/- 0.7 microm, respectively, p < 0.0001). This difference in follicle diameter was mainly due to a larger mean oocyte diameter (primary follicles, stronger vs. weaker, 19.6 +/- 0.6 vs. 31.5 +/- 1.4 microm, p < 0.0001). Oocytes of atretic follicles showed stronger staining with all four CDKIs.


CONCLUSIONS
These preliminary findings suggest that the initiation of oocyte growth, which seems to lead follicle growth, is associated with diminished p16 expression in the mouse ovary. Further studies are needed to investigate the factors that regulate the expression of p16 in the oocyte, which might also govern the initiation of primordial follicle growth.
Bayrak
Aykut
A
Department of Anatomy & Cell Biology, State University of New York Health Science Center, Brooklyn, NY, USA. bayrak@usc.edu
Oktay
Kutluk
K
D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D048429:Cell Size; D003433:Crosses, Genetic; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D004971:Estrus / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D019942:Genes, p16; D006107:Granulosa Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000378:metabolism / Q000648:ultrastructure; D006080:Ovarian Follicle / Q000378:metabolism / Q000648:ultrastructure; D013799:Theca Cells / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; C493968:Cdkn2b protein, mouse; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27