Metabolism and karyotype analysis of oocytes from patients with polycystic ovary syndrome.
BACKGROUND
Polycystic ovary syndrome (PCOS) is associated with metabolic disturbances which include impaired insulin signalling and glucose metabolism in ovarian follicles. The oocyte is metabolically dependent upon its follicle environment during development, but it is unclear whether PCOS or polycystic ovarian (PCO) morphology alone affect oocyte metabolism and energy-demanding processes such as meiosis.


METHODS
Immature human oocytes were donated by PCOS (n = 14), PCO (n = 14) and control (n = 46) patients attending the assisted conception programme at Leeds Teaching Hospitals NHS Trust. Oocytes were cultured individually and carbohydrate metabolism was assessed during overnight in vitro maturation (IVM). Meiotic status was assessed and oocyte intracellular nicotinamide adenine dinucleotide phosphate (NAD(P)H) content and mitochondria activity were measured prior to karyotype analysis by multifluor in situ hybridization.


RESULTS
Patient aetiology had no significant effect on oocyte maturation potential or incidence of numerical chromosome abnormalities (44%), although PCOS and PCO oocytes were more likely to suffer predivision. Group G chromosomes were most likely to be involved in non-disjunction and predivision. PCOS was associated with increased glucose consumption (2.06 +/- 0.43 and 0.54 +/- 0.12 pmol/h for PCOS and control oocytes, respectively) and increased pyruvate consumption (18.4 +/- 1.2 and 13.9 +/- 0.9 pmol/h for PCOS and control oocytes, respectively) during IVM. Prior prescription of metformin significantly attenuated pyruvate consumption by maturing oocytes (8.5 +/- 1.8 pmol/h) from PCOS patients. Oocytes from PCO patients had intermediate metabolism profiles. Higher pyruvate turnover was associated with abnormal oocyte karyotypes (13.4 +/- 1.9 and 19.9 +/- 2.1 pmol/h for normal versus abnormal oocytes, respectively). Similarly, oocyte NAD(P)H content was 1.35-fold higher in abnormal oocytes.


CONCLUSIONS
The chromosomal constitution of in vitro matured oocytes from PCOS is similar to that of controls, but aspects of oocyte metabolism are perturbed by PCOS. Elevated pyruvate consumption was associated with abnormal oocyte karyotype.
Harris
Sarah E
SE
Division of Reproduction and Early Development, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK.
Maruthini
Deivanayagam
D
Tang
Thomas
T
Balen
Adam H
AH
Picton
Helen M
HM
D000328:Adult; D050260:Carbohydrate Metabolism / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000187:drug effects*; D020090:Chromosome Segregation / Q000187:drug effects; D002904:Chromosomes, Human, 21-22 and Y / Q000187:drug effects; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008540:Meiosis / Q000187:drug effects; D008687:Metformin / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism*; D010048:Ovarian Cysts / Q000235:genetics / Q000378:metabolism; D010062:Ovulation Induction / Q000009:adverse effects*; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism*; D032681:Spectral Karyotyping; D020554:Sperm Injections, Intracytoplasmic; D055815:Young Adult
D007004:Hypoglycemic Agents; D009243:NAD; D009249:NADP; D008687:Metformin