Genome instability is increased in lymphocytes of women with polycystic ovary syndrome and is correlated with insulin resistance

Lisa J. Moran, Manny Noakes, Peter M. Clifton, Robert J. Norman, Michael F. Fenech

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and reproductive and metabolic abnormalities. The potential genetic contributors to PCOS are unclear. We tested the hypothesis that genomic instability (chromosome malsegregation and DNA damage) is increased in PCOS. Methods: Overweight age, weight and BMI-matched women with (n = 14) and without (n = 16) PCOS (age 34.2 ± 6.0 years, weight 90.7 ± 14.5 kg, BMI 34.0 ± 5.6 kg/m2, mean ± S.D.) were assessed for chromosome malsegregation (assessed by X chromosome chromogenic in situ hybridisation) and micronucleus frequency (assessed by the cytokinesis block micronucleus index) in lymphocytes. Results: Women with PCOS had significantly elevated genomic instability as demonstrated by a significantly higher number of binucleated lymphocytes containing micronuclei, total number of micronuclei, a higher proportion of aneuploid X chromosome signals (2:1 X and 3:1 X) and a lower proportion of normal X chromosome segregation signals (2:2 X) in binucleated lymphocytes than women without PCOS. Surrogate measures of insulin resistance positively correlated with the proportion of aneuploid cells (2:1; 3:1 X chromosome signals) and inversely with the proportion of normal cells (2:2 X chromosome signals). Conclusion: Women with PCOS display increased genomic instability (higher micronuclei and chromosome malsegregation) compared to women without PCOS and this increase may be related to the insulin resistance phenotype.

Original languageEnglish
Pages (from-to)55-63
Number of pages9
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume639
Issue number1-2
DOIs
Publication statusPublished - 1 Mar 2008

Keywords

  • Genomic instability
  • Insulin resistance
  • Micronucleus index
  • Obesity
  • Polycystic ovary syndrome
  • X chromosome aneuploidy

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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