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This version published online on August 14, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-0729
A more recent version of this article appeared on November 1, 2007
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Submitted on March 29, 2007
Accepted on August 3, 2007

Abnormal Preantral Folliculogenesis in Polycystic Ovaries is Associated with Increased Granulosa Cell Division

Sharron A. Stubbs, Jaroslav Stark, Stephen M. Dilworth, Stephen Franks, and Kate Hardy*

Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London, W12 0NN, UK; Department of Mathematics, Imperial College London, London SW7 2AZ, UK; Department of Metabolic Medicine, Division of Investigative Science, Imperial College London, Hammersmith Hospital, London, W12 0NN, UK

* To whom correspondence should be addressed. E-mail: k.hardy{at}imperial.ac.uk.

Context: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women but its etiology remains obscure. Recent data suggest that an intrinsic abnormality of early follicle development in the ovary is key to the pathogenesis of PCOS. We have recently found that in PCOS the proportion of primordial follicles is decreased with a reciprocal increase in the proportion of primary follicles.

Objective: To examine whether the accelerated transition of follicles from primordial to primary stages in polycystic ovaries is due to increased granulosa cell (GC) division.

Design: Comparison of expression of minichromosome maintenance protein 2 (MCM2; present in the nuclei of cells which are licensed to divide) in archive tissue from normal and polycystic ovaries.

Setting: Laboratory-based study.

Patients: 16 women with regular cycles (6 with normal and 10 with polycystic ovaries) and 5 anovulatory women with polycystic ovaries (anovPCO), classified histologically, with reference to menstrual history and ultrasound.

Main outcome measure: Presence of MCM2 expression in GCs of 1371 follicles.

Results: GC proliferation was increased in anovPCO compared with both normal and ovPCO, with an increased proportion of preantral follicles with MCM2-positive GCs (P ≤ 0.015). The number of GCs differed significantly between the three types of ovary at the transitional (P = 0.013) and primary (P = 0.0096) stages. This was accompanied by an altered relationship (P < 0.0001) between oocyte growth and GC division/cuboidalization.

Conclusions: These findings provide evidence for increased GC proliferation in early growing follicles in PCOS. This offers an explanation for the increased proportion of primary follicles in PCOS.


Key words: Ovary • PCOS • MCM2 • Follicle • Folliculogenesis • Immunohistochemistry




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