The expression of cyclin-dependent kinase inhibitors p15, p16, p21, and p27 during ovarian follicle growth initiation in the mouse

Aykut Bayrak,Kutluk Oktay

doi:10.1186/1477-7827-1-41

Abstract

BackgroundCyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs).MethodIn 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).ResultsExpression 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 μm, 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 μm, p < 0.0001). Oocytes of atretic follicles showed stronger staining with all four CDKIs.ConclusionsThese 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.

Highlights

The onset of growth of an individual primordial follicle is unpredictable; some beginning shortly after formation while others may remain "quiescent" for many years
Oocytes of atretic follicles showed stronger staining with all four cyclin dependent kinase inhibitors (CDKIs)
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

Summary

Introduction

The onset of growth of an individual primordial follicle is unpredictable; some beginning shortly after formation while others may remain "quiescent" for many years. We previously showed that the Proliferating Cell Nuclear Antigen (PCNA) is expressed in the rodent ovarian follicles at the earliest sign of growth [1]. PCNA is a co-factor of cyclin-D and it makes a complex with cyclin-D, a cyclin dependent kinase (CDK), and a cyclin dependent kinase inhibitor (CDKI). The progression of cells through the cell cycle is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs). The sequential activation of the members of this family and their phosphorylation of certain substrates promotes the progression through the cell cycle. Cyclins regulate the cell cycle in association with cyclin dependent kinases (CDKs). CDKs are under inhibitory control of cyclin dependent kinase inhibitors (CDKIs)

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