title: Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women.
abstract: BACKGROUND
  Obese women experience longer times to conception, even if they are young and cycling regularly, which is suggestive of alterations in ovarian function during the periconceptual period.
  
  
  OBJECTIVE
  This study sought to determine whether there are alterations in the preovulatory follicular environment that are likely to influence oocyte developmental competence.
  
  
  METHODS
  Women attending a private infertility clinic were categorized into body mass index (BMI) groups of moderate (n = 33; BMI 20-24.9 kg/m(2)), overweight (n = 31; BMI 25-29.9 kg/m(2)), and obese (n =32; BMI >or=30 kg/m(2)).
  
  
  METHODS
  For each patient, follicular fluid was recovered from single follicles at oocyte retrieval, granulosa cells were pooled from multiple follicular aspirates and cumulus cells were pooled after separation from the oocytes.
  
  
  METHODS
  Follicle fluid was assayed for hormones and metabolites. Granulosa and cumulus cells were analyzed for mRNA expression of insulin signaling components (IRS-2 and Glut4), glucose-regulated genes (ChREBP, ACC, and FAS) and insulin-regulated genes (SREBP-1, CD36, and SR-BI) associated with obesity/insulin resistance.
  
  
  RESULTS
  Increasing BMI was associated with increased follicular fluid insulin (P < 0.001), lactate (P = 0.01), triglycerides (P = 0.0003), and C-reactive protein (P < 0.0001) as well as decreased SHBG (P = 0.001). IRS-2, Glut4, ChREBP, and SREBP exhibited cell-type-specific expression but were not affected by BMI. CD36 and SRBI mRNA were modestly altered in granulosa cells of obese compared with moderate-weight women.
  
  
  CONCLUSIONS
  Obese women exhibit an altered ovarian follicular environment, particularly increased metabolite, C-reactive protein, and androgen activity levels, which may be associated with poorer reproductive outcomes typically observed in these patients.
authors.affiliation: The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, 5005 Australia. rebecca.robker@adelaide.edu.au
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Robker
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Akison
authors.forename: Brenton D
authors.initials: BD
authors.lastname: Bennett
authors.forename: Penny N
authors.initials: PN
authors.lastname: Thrupp
authors.forename: Lindsay R
authors.initials: LR
authors.lastname: Chura
authors.forename: Darryl L
authors.initials: DL
authors.lastname: Russell
authors.forename: Michelle
authors.initials: M
authors.lastname: Lane
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Norman
mesh_terms: D000328:Adult; D000728:Androgens / Q000378:metabolism; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics* / Q000502:physiology*; D002097:C-Reactive Protein / Q000378:metabolism; D054885:Cumulus Cells / Q000378:metabolism; D005260:Female; D015571:Follicular Fluid / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006107:Granulosa Cells / Q000378:metabolism; D006728:Hormones / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D010053:Ovary / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D012098:Reproduction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000728:Androgens; D006728:Hormones; D012313:RNA; D002097:C-Reactive Protein