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This version published online on February 17, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-2648
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Submitted on December 4, 2008
Accepted on February 5, 2009

Obese Women Exhibit Differences in Ovarian Metabolites, Hormones, and Gene Expression Compared to Moderate Weight Women

Rebecca L. Robker*, Lisa K. Akison, Brenton D. Bennett, Penny N. Thrupp, Lindsay R. Chura, Darryl L. Russell, Michelle Lane, and Robert J. Norman

The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia

* To whom correspondence should be addressed. E-mail: rebecca.robker{at}adelaide.edu.au.

Context: 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 peri-conceptual period.

Objective: This study sought to determine if there are alterations in the pre-ovulatory follicular environment that are likely to influence oocyte developmental competence.

Design, Setting and Participants: Women attending a private infertility clinic were categorized into Body Mass Index (kg/m2) groups of moderate (n= 33; BMI 20–24.9), overweight (n= 31; BMI 25–29.9) and obese (n=32; BMI ≥30).

Intervention: 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 following separation from the oocytes.

Main Outcome Measures: Follicle fluid was assayed for hormones and metabolites. Granulosa and cumulus cells were analysed for mRNA expression of insulin signalling components (IRS-2, Glut4), glucose regulated genes (ChREBP, ACC, FAS) and insulin regulated genes (SREBP-1, CD36, 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 to moderate weight women.

Conclusions: Obese women exhibit an altered ovarian follicular environment, particularly increased metabolite, CRP and androgen activity levels, which may be associated with poorer reproductive outcomes typically observed in these patients.


Key words: obesity • ovary • granulosa cell • cumulus cell • follicular fluid







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