title: Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation.
abstract: OBJECTIVE
  To detect expression of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) in oocytes, and their receptor type 2 receptor for BMPs (BMPR2) in cumulus cells in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF), and determine if BMPR2, BMP15, and GDF9 expression correlate with hyperandrogenism in FF of PCOS patients.
  
  
  METHODS
  Prospective case-control study. Eighteen MII-oocytes and their respective cumulus cells were obtained from 18 patients with PCOS, and 48 MII-oocytes and cumulus cells (CCs) from 35 controls, both subjected to controlled ovarian hyperstimulation (COH), and follicular fluid (FF) was collected from small (10-14 mm) and large (>18 mm) follicles. RNeasy Micro Kit (Qiagen) was used for RNA extraction and gene expression was quantified in each oocyte individually and in microdissected cumulus cells from cumulus-oocyte complexes retrieved from preovulatory follicles using qRT-PCR. Chemiluminescence and RIA assays were used for hormone assays.
  
  
  RESULTS
  BMP15 and GDF9 expression per oocyte was higher among women with PCOS than the control group. A positive correlation was found between BMPR2 transcripts and hyperandrogenism in FF of PCOS patients. Progesterone values in FF were lower in the PCOS group.
  
  
  CONCLUSIONS
  We inferred that BMP15 and GDF9 transcript levels increase in mature PCOS oocytes after COH, and might inhibit the progesterone secretion by follicular cells in PCOS follicles, preventing premature luteinization in cumulus cells. BMPR2 expression in PCOS cumulus cells might be regulated by androgens.
authors: Department of Gynecology and Obstetrics - Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors: Luciana Ochuiuto Teixeira
authors: LO
authors: de Resende
authors: Alessandra Aparecida
authors: AA
authors: Vireque
authors: Laura Ferreira
authors: LF
authors: Santana
authors: Daniel Antunes
authors: DA
authors: Moreno
authors: Ana Carolina Japur
authors: AC
authors: de Sá Rosa e Silva
authors: Rui Alberto
authors: RA
authors: Ferriani
authors: Carlos Alberto
authors: CA
authors: Scrideli
authors: Rosana Maria
authors: RM
authors: Reis
mesh_terms: D000328:Adult; D055430:Bone Morphogenetic Protein 15 / Q000235:genetics*; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000032:analysis*; D016022:Case-Control Studies; D054885:Cumulus Cells / Q000502:physiology*; D005260:Female; D005307:Fertilization in Vitro; D015571:Follicular Fluid; D015870:Gene Expression; D055429:Growth Differentiation Factor 9 / Q000235:genetics*; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics; D009865:Oocytes / Q000502:physiology*; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000473:pathology*; D011247:Pregnancy; D018873:Pregnancy Rate; D011374:Progesterone / Q000032:analysis / Q000378:metabolism; D059010:Single-Cell Analysis
chemical_list: D055430:Bone Morphogenetic Protein 15; C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; D011374:Progesterone; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II