Abnormal preantral folliculogenesis in polycystic ovaries is associated with increased granulosa cell division

Context: Polycystic ovary syndrome ( PCOS) is the most common 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: Our aim was to examine whether the accelerated transition of follicles from primordial to primary stages in polycystic ovaries ( PCO) is due to increased granulosa cell ( GC) division. Design: This study is a comparison of expression of minichromosome maintenance protein 2 ( MCM2) ( present in the nuclei of cells that are licensed to divide) in archive tissue from normal and PCO. Setting: This is a laboratory- based study. Patients: There were 16 women with regular cycles ( six with normal and 10 with PCO) and five anovulatory women with PCO, classified histologically, with reference to menstrual history and ultrasound. Main Outcome Measures: The presence of MCM2 expression in the GCs of 1371 follicles was determined. Results: GC proliferation was increased in anovulatory PCO compared with both normal and ovulatory PCO, with an increased proportion of preantral follicles with MCM2- positive GCs ( P <= 0.015). The number of GCs differed significantly among 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.