title: Oxygen-regulated gene expression in murine cumulus cells.
abstract: Oxygen is an important component of the environment of the cumulus-oocyte complex (COC), both in vivo within the ovarian follicle and during in vitro oocyte maturation (IVM). Cumulus cells have a key role in supporting oocyte development, and cumulus cell function and gene expression are known to be altered when the environment of the COC is perturbed. Oxygen-regulated gene expression is mediated through the actions of the transcription factors, the hypoxia-inducible factors (HIFs). In the present study, the effect of oxygen on cumulus cell gene expression was examined following in vitro maturation of the murine COC at 2%, 5% or 20% oxygen. Increased expression of HIF-responsive genes, including glucose transporter-1, lactate dehydrogenase A and BCL2/adenovirus E1B interacting protein 3, was observed in cumulus cells matured at 2% or 5%, compared with 20% oxygen. Stabilisation of HIF1α protein in cumulus cells exposed to low oxygen was confirmed by western blot and HIF-mediated transcriptional activity was demonstrated using a transgenic mouse expressing green fluorescent protein under the control of a promoter containing hypoxia response elements. These results indicate that oxygen concentration influences cumulus cell gene expression and support a role for HIF1α in mediating the cumulus cell response to varying oxygen.
authors.affiliation: The Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Kind
authors.affiliation: The Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Kimberley K Y
authors.initials: KK
authors.lastname: Tam
authors.affiliation: The Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Banwell
authors.affiliation: The Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Gauld
authors.affiliation: The Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Darryl L
authors.initials: DL
authors.lastname: Russell
authors.affiliation: The Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Macpherson
authors.affiliation: The Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Brown
authors.affiliation: The Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Frank
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Peet
authors.affiliation: The Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Thompson
mesh_terms: D017501:Adenovirus E1B Proteins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015153:Blotting, Western; D054885:Cumulus Cells / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000502:physiology; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D059471:In Vitro Oocyte Maturation Techniques / Q000379:methods*; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D051379:Mice; D008822:Mice, Transgenic; D010100:Oxygen / Q000494:pharmacology*
chemical_list: D017501:Adenovirus E1B Proteins; D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D051272:Glucose Transporter Type 1; D049452:Green Fluorescent Proteins; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D010100:Oxygen