title: Multidrug-resistant transport activity protects oocytes from chemotherapeutic agents and changes during oocyte maturation.
abstract: OBJECTIVE
  To determine the multidrug-resistant transporter (MDR) activity in oocytes and their potential role in oocyte susceptibility to chemotherapy.
  
  
  METHODS
  Experimental laboratory study.
  
  
  METHODS
  University and academic center for reproductive medicine.
  
  
  METHODS
  Women with eggs retrieved for intracytoplasmic sperm injection cycles and adult female FVBN and B6C3F1 mouse strains.
  
  
  METHODS
  Inhibition of MDR activity in oocytes.
  
  
  METHODS
  Efflux activity of MDRs with the use of quantitative fluorescent dye efflux, and oocyte cell death when exposed to chemotherapy.
  
  
  RESULTS
  Oocytes effluxed fluorescent reporters, and this activity was significantly reduced in the presence of the MDR inhibitor PSC 833. Geminal vesicle oocytes were more efficient at efflux than metaphase 2 oocytes. Human oocytes exposed to cyclophosphamide and PSC 833 showed cell death with the use of two different viability assays compared with control samples and those exposed to cyclophosphamide alone. Immunoblots detected MDR-1 in all oocytes, with the greatest accumulation in the geminal vesicle stage.
  
  
  CONCLUSIONS
  Oocytes have a vast repertoire of active MDRs. The implications of this study are that these protective mechanisms are important during oogenesis and that these activities change with maturation, increasing susceptibility to toxicants. Future directions may exploit the up-regulation of these transporters during gonadotoxic therapy.
authors: Division of Reproductive Endocrinology and Infertility, Women and Infants Hospital, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island.
authors: Lynae M
authors: LM
authors: Brayboy
authors: Nathalie
authors: N
authors: Oulhen
authors: Jeannine
authors: J
authors: Witmyer
authors: Jared
authors: J
authors: Robins
authors: Sandra
authors: S
authors: Carson
authors: Gary M
authors: GM
authors: Wessel
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity*; D001692:Biological Transport; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000378:metabolism / Q000633:toxicity*; D003524:Cyclosporins / Q000494:pharmacology; D019610:Cytoprotection; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009866:Oogenesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D003524:Cyclosporins; D005456:Fluorescent Dyes; D012333:RNA, Messenger; D003520:Cyclophosphamide; C070272:valspodar
keywords: ATP-binding cassette (ABC); P-glycoprotein (MDR-1); chemotherapy; multidrug-resistant (MDR) transporter; oocyte
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