OBJECTIVE: To determine the multidrug-resistant transporter (MDR) activity in oocytes and their potential role in oocyte susceptibility to chemotherapy. DESIGN: Experimental laboratory study. SETTING: University and academic center for reproductive medicine. SUBJECT(S): Women with eggs retrieved for intracytoplasmic sperm injection cycles and adult female FVBN and B6C3F1 mouse strains. INTERVENTION(S): Inhibition of MDR activity in oocytes. MAIN OUTCOME MEASURE(S): Efflux activity of MDRs with the use of quantitative fluorescent dye efflux, and oocyte cell death when exposed to chemotherapy. RESULT(S): 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. CONCLUSION(S): 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.
OBJECTIVE: To determine the multidrug-resistant transporter (MDR) activity in oocytes and their potential role in oocyte susceptibility to chemotherapy. DESIGN: Experimental laboratory study. SETTING: University and academic center for reproductive medicine. SUBJECT(S): Women with eggs retrieved for intracytoplasmic sperm injection cycles and adult female FVBN and B6C3F1 mouse strains. INTERVENTION(S): Inhibition of MDR activity in oocytes. MAIN OUTCOME MEASURE(S): Efflux activity of MDRs with the use of quantitative fluorescent dye efflux, and oocyte cell death when exposed to chemotherapy. RESULT(S): 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. CONCLUSION(S): 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: Yvonne A R White; Dori C Woods; Yasushi Takai; Osamu Ishihara; Hiroyuki Seki; Jonathan L Tilly Journal: Nat Med Date: 2012-02-26 Impact factor: 53.440
Authors: Haley Clark; Laura O Knapik; Zijing Zhang; Xiaotian Wu; Mandar T Naik; Nathalie Oulhen; Gary M Wessel; Lynae M Brayboy Journal: Sci Rep Date: 2019-07-03 Impact factor: 4.379
Authors: N Spears; F Lopes; A Stefansdottir; V Rossi; M De Felici; R A Anderson; F G Klinger Journal: Hum Reprod Update Date: 2019-11-05 Impact factor: 15.610
Authors: Jasmine L Chiang; Pallavi Shukla; Kelly Pagidas; Noha S Ahmed; Srinivasu Karri; Deidre D Gunn; William W Hurd; Keshav K Singh Journal: Ageing Res Rev Date: 2020-09-04 Impact factor: 11.788