title: Alteration of energy metabolism gene expression in cumulus cells affects oocyte maturation via MOS-mitogen-activated protein kinase pathway in dairy cows with an unfavorable "Fertil-" haplotype of one female fertility quantitative trait locus.
abstract: Prim'Holstein heifers selected for the "Fertil-" homozygous haplotype of QTL-Female-Fert ility-BTA3 showed a greater rate of early pregnancy failure and slower embryo development after IVM suggesting lower oocyte quality than those selected for "Fertile+". We aimed to ascertain intrafollicular factors related to lower oocyte quality in "Fertil-" cows. Analysis of individual oocytes showed meiotic progression delay in "Fertil-" compared with "Fertil+" dairy cows after in vivo maturation and IVM (P < 0.05). Expression of several genes localized to QTL-F-Fert-BTA3 or related to meiosis and mitogen-activated protein kinase pathway was analyzed in individual metaphase-II oocytes using reverse transcription- real-time polymerase chain reaction. Energy metabolism, apoptosis, extracellular matrix, and QTL-F-Fert-BTA3 genes were analyzed in surrounding cumulus cells (CC). In vivo, a significant decrease in prostaglandin synthase PTGES1 and PTGS2 expression coupled with lower PTGS2 protein abundance in CC and reduced expression of MOS in enclosed metaphase-II oocytes from "Fertil-" cows was observed. IVM strongly deregulated gene expression in CC and in oocytes compared with in vivo; nevertheless, differential expression of several genes including PEX19, NAMPT and MOS was observed between the two haplotypes. During IVM, PTGS2 activity inhibitor NS398 (50 μM) led to lower expression of fatty acid synthase (FASN) in CC and of MOS in treated metaphase-II oocytes. Using immunofluorescence, MOS protein was localized to a midbody-like contractile ring separating the polar body from the ooplasm, suggesting a role in the terminal stage of oocyte maturation. Our results suggest that factors involved in prostaglandin synthesis and lipid metabolism in CC could impair oocyte maturation, and might be involved in the reduced fertility of "Fertil-" cows.
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France; CNRS UMR7247, Nouzilly, France; Université François Rabelais de Tours, Tours, France; IFCE, Nouzilly, France.
authors.forename: Daphné
authors.initials: D
authors.lastname: Brisard
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France; CNRS UMR7247, Nouzilly, France; Université François Rabelais de Tours, Tours, France; IFCE, Nouzilly, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Desmarchais
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France; CNRS UMR7247, Nouzilly, France; Université François Rabelais de Tours, Tours, France; IFCE, Nouzilly, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Touzé
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France; CNRS UMR7247, Nouzilly, France; Université François Rabelais de Tours, Tours, France; IFCE, Nouzilly, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Lardic
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France; CNRS UMR7247, Nouzilly, France; Université François Rabelais de Tours, Tours, France; IFCE, Nouzilly, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Freret
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France; CNRS UMR7247, Nouzilly, France; Université François Rabelais de Tours, Tours, France; IFCE, Nouzilly, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Elis
authors.affiliation: INRA, UMR1198 Biologie du Développement et Reproduction, Jouy-en-Josas, France; ENVA, Maisons-Alfort, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Nuttinck
authors.affiliation: INRA, UMR1198 Biologie du Développement et Reproduction, Jouy-en-Josas, France; ENVA, Maisons-Alfort, France.
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Camous
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France; CNRS UMR7247, Nouzilly, France; Université François Rabelais de Tours, Tours, France; IFCE, Nouzilly, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Dupont
authors.affiliation: INRA, UMR85 Physiologie de la Reproduction et des Comportements, Nouzilly, France; CNRS UMR7247, Nouzilly, France; Université François Rabelais de Tours, Tours, France; IFCE, Nouzilly, France. Electronic address: svetlana.uzbekova@tours.inra.fr.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Uzbekova
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000032:analysis; D002417:Cattle / Q000235:genetics / Q000378:metabolism*; D054885:Cumulus Cells / Q000201:enzymology / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D004958:Estradiol / Q000032:analysis; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D006239:Haplotypes / Q000235:genetics / Q000502:physiology; D020738:Leptin / Q000032:analysis; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000032:analysis; D040641:Quantitative Trait Loci / Q000235:genetics / Q000502:physiology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D020738:Leptin; D011374:Progesterone; D004958:Estradiol; D012313:RNA; D054304:Anti-Mullerian Hormone; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
keywords: Cumulus; Dairy cow; Fertility; MOS; Oocyte maturation; Prostaglandin Synthase 2