title: Enhanced Inflammatory Transcriptome in the Granulosa Cells of Women With Polycystic Ovarian Syndrome.
abstract: Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of reproductive-aged women, is associated with systemic low-grade inflammation.
  
  
  
  We propose that increased or altered intrafollicular inflammatory reactions also occur in periovulatory follicles of PCOS patients.
  
  
  
  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.
  
  
  
  This was a university-based study.
  
  
  
  Twenty-one PCOS and 45 control patients were recruited: demographic, hormone, body mass index, and pregnancy outcomes were abstracted from patient data files.
  
  
  
  GC cytokine/chemokine mRNAs 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.
  
  
  
  Relative serum/FF cytokine levels and GC cytokine expression before and after culture were compared and related to body mass index.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Molecular and Cellular Biology (J.A., Z.L., Y.A.R., J.R.) and Division of Reproductive Endocrinology and Infertility (J.A., C.V., W.G.), Baylor College of Medicine, and M. D. Anderson Cancer Center (W.Z.), Houston, Texas 77030; Fertility Specialists of Houston (Z.L., W.-S.W.), Houston, Texas; 77030 and CReATe Fertility Center (S.K., C.L.), Toronto, Canada M5G 1N8.
authors.forename: Jaye
authors.initials: J
authors.lastname: Adams
authors.affiliation: Department of Molecular and Cellular Biology (J.A., Z.L., Y.A.R., J.R.) and Division of Reproductive Endocrinology and Infertility (J.A., C.V., W.G.), Baylor College of Medicine, and M. D. Anderson Cancer Center (W.Z.), Houston, Texas 77030; Fertility Specialists of Houston (Z.L., W.-S.W.), Houston, Texas; 77030 and CReATe Fertility Center (S.K., C.L.), Toronto, Canada M5G 1N8.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Molecular and Cellular Biology (J.A., Z.L., Y.A.R., J.R.) and Division of Reproductive Endocrinology and Infertility (J.A., C.V., W.G.), Baylor College of Medicine, and M. D. Anderson Cancer Center (W.Z.), Houston, Texas 77030; Fertility Specialists of Houston (Z.L., W.-S.W.), Houston, Texas; 77030 and CReATe Fertility Center (S.K., C.L.), Toronto, Canada M5G 1N8.
authors.forename: Yi Athena
authors.initials: YA
authors.lastname: Ren
authors.affiliation: Department of Molecular and Cellular Biology (J.A., Z.L., Y.A.R., J.R.) and Division of Reproductive Endocrinology and Infertility (J.A., C.V., W.G.), Baylor College of Medicine, and M. D. Anderson Cancer Center (W.Z.), Houston, Texas 77030; Fertility Specialists of Houston (Z.L., W.-S.W.), Houston, Texas; 77030 and CReATe Fertility Center (S.K., C.L.), Toronto, Canada M5G 1N8.
authors.forename: Wan-Song
authors.initials: WS
authors.lastname: Wun
authors.affiliation: Department of Molecular and Cellular Biology (J.A., Z.L., Y.A.R., J.R.) and Division of Reproductive Endocrinology and Infertility (J.A., C.V., W.G.), Baylor College of Medicine, and M. D. Anderson Cancer Center (W.Z.), Houston, Texas 77030; Fertility Specialists of Houston (Z.L., W.-S.W.), Houston, Texas; 77030 and CReATe Fertility Center (S.K., C.L.), Toronto, Canada M5G 1N8.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Molecular and Cellular Biology (J.A., Z.L., Y.A.R., J.R.) and Division of Reproductive Endocrinology and Infertility (J.A., C.V., W.G.), Baylor College of Medicine, and M. D. Anderson Cancer Center (W.Z.), Houston, Texas 77030; Fertility Specialists of Houston (Z.L., W.-S.W.), Houston, Texas; 77030 and CReATe Fertility Center (S.K., C.L.), Toronto, Canada M5G 1N8.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Kenigsberg
authors.affiliation: Department of Molecular and Cellular Biology (J.A., Z.L., Y.A.R., J.R.) and Division of Reproductive Endocrinology and Infertility (J.A., C.V., W.G.), Baylor College of Medicine, and M. D. Anderson Cancer Center (W.Z.), Houston, Texas 77030; Fertility Specialists of Houston (Z.L., W.-S.W.), Houston, Texas; 77030 and CReATe Fertility Center (S.K., C.L.), Toronto, Canada M5G 1N8.
authors.forename: Clifford
authors.initials: C
authors.lastname: Librach
authors.affiliation: Department of Molecular and Cellular Biology (J.A., Z.L., Y.A.R., J.R.) and Division of Reproductive Endocrinology and Infertility (J.A., C.V., W.G.), Baylor College of Medicine, and M. D. Anderson Cancer Center (W.Z.), Houston, Texas 77030; Fertility Specialists of Houston (Z.L., W.-S.W.), Houston, Texas; 77030 and CReATe Fertility Center (S.K., C.L.), Toronto, Canada M5G 1N8.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Valdes
authors.affiliation: Department of Molecular and Cellular Biology (J.A., Z.L., Y.A.R., J.R.) and Division of Reproductive Endocrinology and Infertility (J.A., C.V., W.G.), Baylor College of Medicine, and M. D. Anderson Cancer Center (W.Z.), Houston, Texas 77030; Fertility Specialists of Houston (Z.L., W.-S.W.), Houston, Texas; 77030 and CReATe Fertility Center (S.K., C.L.), Toronto, Canada M5G 1N8.
authors.forename: William
authors.initials: W
authors.lastname: Gibbons
authors.affiliation: Department of Molecular and Cellular Biology (J.A., Z.L., Y.A.R., J.R.) and Division of Reproductive Endocrinology and Infertility (J.A., C.V., W.G.), Baylor College of Medicine, and M. D. Anderson Cancer Center (W.Z.), Houston, Texas 77030; Fertility Specialists of Houston (Z.L., W.-S.W.), Houston, Texas; 77030 and CReATe Fertility Center (S.K., C.L.), Toronto, Canada M5G 1N8.
authors.forename: JoAnne
authors.initials: J
authors.lastname: Richards
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid / Q000378:metabolism*; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008184:Luteal Cells / Q000378:metabolism* / Q000473:pathology; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger