Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 101, Issue 9, Pages 3459-3468Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2015-4275
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Funding
- National Institutes of Health [NIH-HD-16229, NIH-HD-07495]
- Baylor College of Medicine departmental obstetrics/gynecology
- Department of Molecular and Cellular Biology
- Department of Obstetrics and Gynecology/Division of Reproductive Endocrinology and Infertility
- Genomic and RNA Profiling Core, Clinical Scientist Training Program, University of Virginia
- Center for Research in Reproduction, Ligand Assay and Analysis Core
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (Specialized Cooperative Centers Program in Reproduction and Infertility Research) [U54-HD028934]
- Fertility Specialists of Houston (Houston, Texas)
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Context: Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of reproductive-aged women, is associated with systemic low-grade inflammation. Objective: We propose that increased or altered intrafollicular inflammatory reactions also occur in periovulatory follicles of PCOS patients. Design: Gene profiling and quantitative PCR (qPCR) analyses in granulosa-lutein cells (GCs) collected from PCOS and non-PCOS women undergoing in vitro fertilization were compared with serum and follicular fluid (FF) levels of cytokines and chemokines. Setting: This was a university-based study. Patients: Twenty-one PCOS and 45 control patients were recruited: demographic, hormone, body mass index, and pregnancy outcomes were abstracted from patient data files. Interventions: GC cytokine/chemokinem RNAs were identified and analyzed by gene-chip microarrays/qPCR before and after culture with human chorionic gonadotropin, DHT, IL-6, or IL-8; serum/FF cytokine levels were also analyzed. Main Outcome Measures: Relative serum/FF cytokine levels and GC cytokine expression before and after culture were compared and related to body mass index. Results: The following results were found: 1) PCOS GCs express elevated transcripts encoding cytokines, chemokines, and immune cell markers, 2) based on gene profiling and qPCR analyses, obese PCOS patients define a distinct PCOS disease subtype with the most dramatic increases in proinflammatory and immune-related factors, and 3) human chorionic gonadotropin and DHT increased cytokine production in cultured GCs, whereas cytokines augmented cytokine and vascular genes, indicating that hyperandrogenism/elevated LH and obesity in PCOS women augment intrafollicular cytokine production. Conclusions: Intrafollicular androgens and cytokines likely comprise a local regulatory loop that impacts GC expression of cytokines and chemokines and the presence of immune cells; this loop is further enhanced in the obese PCOS subtype.
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