title: Gene expression of cumulus cells in women with poor ovarian response after dehydroepiandrosterone supplementation.
abstract: OBJECTIVE
  Our previous study showed the potential benefits of dehydroepiandrosterone (DHEA) supplementation in women with a poor ovarian response (POR). Because the connection between cumulus cells (CCs) and oocytes is a key step for oocyte maturation, we supposed that altered gene expression of CCs in women with POR after DHEA supplementation might favor oocyte maturation.
  
  
  METHODS
  Women with POR treated with flexible daily gonadotropin-releasing hormone antagonist in vitro fertilization (IVF) cycles at The Reproductive Center in Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan between January 2013 and October 2013 were enrolled for this prospective study. CCs were isolated during IVF before and after DHEA (CPH-Formulation, Oakdale, CA, USA) supplementation. Nine genes of isolated CCs, including hyaluronan synthase (HAS2), versican (VCAN), thrombospondin 1 (THBS1), runt-related transcription factor 2 (RUNX2), chromobox homolog 3 (CBX3), tripartite motif-containing 28 (TRIM28), B-cell lymphoma 2 (BCL2), BCL2-associated X protein (BAX), and ankyrin repeat domain 57 (ANKRD57), were compared.
  
  
  RESULTS
  There was a significant difference in the expression of genes in women with POR before and after DHEA supplementation (all p < 0.05). All genes related to extracellular matrix (ECM) formation, including HAS2, VCAN, and THBS1, were upregulated. By contrast, all genes involving cell development, differentiation, and apoptosis regulation were downregulated. Unknown function gene ANKRD57 was also downregulated after DHEA supplementation. Although expressions of both BCL2 and BAX were decreased in women with POR after DHEA supplementation compared to those before treatment, the ratio of BCL2 and BAX was significantly increased in women with POR after DHEA supplementation, suggesting that DHEA supplementation might activate the antiapoptosis process of CCs, which might be beneficial to the improvement of ovarian function in women with POR.
  
  
  CONCLUSIONS
  The study showed that DHEA therapy positively affected the gene expression of CCs in women with POR, and provided evidence to support the positive effect of DHEA supplementation on women with POR.
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung County, Taiwan.
authors.forename: Kuan-Hao
authors.initials: KH
authors.lastname: Tsui
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Su-Ao and Yuanshan Branch, Ilan, Taiwan.
authors.forename: Li-Te
authors.initials: LT
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Gynecology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Huann-Cheng
authors.initials: HC
authors.lastname: Horng
authors.affiliation: Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: Renin
authors.initials: R
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University Hospital, Ilan, Taiwan.
authors.forename: Ben-Shian
authors.initials: BS
authors.lastname: Huang
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan. Electronic address: tusya@mail.nsysu.edu.tw.
authors.forename: Jiin-Tsuey
authors.initials: JT
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Gynecology, Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Yang-Ming University Hospital, Ilan, Taiwan; Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address: phwang@vghtpe.gov.tw.
authors.forename: Peng-Hui
authors.initials: PH
authors.lastname: Wang
mesh_terms: D054885:Cumulus Cells / Q000187:drug effects*; D003687:Dehydroepiandrosterone / Q000494:pharmacology / Q000627:therapeutic use*; D019587:Dietary Supplements; D015536:Down-Regulation; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology / Q000627:therapeutic use*; D005307:Fertilization in Vitro; D005819:Genetic Markers; D006801:Humans; D007247:Infertility, Female / Q000235:genetics / Q000628:therapy*; D010062:Ovulation Induction / Q000379:methods*; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D005300:Fertility Agents, Female; D005819:Genetic Markers; D003687:Dehydroepiandrosterone
keywords: DHEA; cumulus cells; dehydroepiandrosterone; diminished ovarian reserve; poor ovarian response