title: The role of nitric oxide in the outgrowth of trophoblast cells on human umbilical vein endothelial cells.
abstract: OBJECTIVE
  Embryo implantation is a complex process that requires coordinated trophoblast-endometrial interactions. Previous studies demonstrated that the identification of nitric oxide synthase (NOS) in trophoblast cells and the remodeling of the implantation process by nitric oxide (NO) support the important role of NO during implantation. However, the role of NO in trophoblast-endometrial interactions is unclear and is therefore examined in this study.
  
  
  METHODS
  We cocultured BeWo trophoblast spheroids with human umbilical vein endothelial cell (HUVEC) monolayers to mimic the trophoblast-endometrial interaction. N(ω)-Nitro-l-arginine methyl ester hydrochloride (l-NAME), a competitive inhibitor of NOS, and sodium nitroprusside (SNP), an NO donor, were used to test the role of NO in the trophoblast-endometrial interaction.
  
  
  RESULTS
  l-NAME diminished spheroid expansion on HUVEC monolayers in a concentration-dependent manner (p < 0.05). However, trophoblast spreading on HUVEC-free culture surfaces was unaffected by l-NAME treatment (p > 0.05). Significant suppression of spheroid expansion was found at the higher dose (1mM) of SNP (p < 0.05).
  
  
  CONCLUSIONS
  NO may be needed in the process of implantation, and an adequate but not overly NO-containing environment might be an important factor for successful implantation. This finding is worthy of further investigation.
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, 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, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsin-Yang
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Biological Science, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Jiin-Tsuey
authors.initials: JT
authors.lastname: Cheng
authors.affiliation: Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yen-Jen
authors.initials: YJ
authors.lastname: Sung
authors.affiliation: Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ming-Shyen
authors.initials: MS
authors.lastname: Yen
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Shie-Liang Edmond
authors.initials: SL
authors.lastname: Hsieh
authors.affiliation: Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei, Taiwan; Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan. Electronic address: phwang@vghtpe.tw.
authors.forename: Peng-Hui
authors.initials: PH
authors.lastname: Wang
mesh_terms: D002450:Cell Communication / Q000187:drug effects*; D018920:Coculture Techniques; D042783:Endothelial Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D018874:Spheroids, Cellular / Q000187:drug effects / Q000502:physiology*; D014327:Trophoblasts / Q000187:drug effects / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
keywords: endometrium; implantation; nitric oxide; trophoblast