title: CHEMERIN (RARRES2) decreases in vitro granulosa cell steroidogenesis and blocks oocyte meiotic progression in bovine species.
abstract: CHEMERIN, or RARRES2, is a new adipokine that is involved in the regulation of adipogenesis, energy metabolism, and inflammation. Recent data suggest that it also plays a role in reproductive function in rats and humans. Here we studied the expression of CHEMERIN and its three receptors (CMKLR1, GPR1, and CCRL2) in the bovine ovary and investigated the in vitro effects of this hormone on granulosa cell steroidogenesis and oocyte maturation. By RT-PCR, immunoblotting, and immunohistochemistry, we found CHEMERIN, CMKLR1, GPR1, and CCRL2 in various ovarian cells, including granulosa and theca cells, corpus luteum, and oocytes. In cultured bovine granulosa cells, INSULIN, IGF1, and two insulin sensitizers-metformin and rosiglitazone-increased rarres2 mRNA expression whereas they decreased cmklr1, gpr1, and cclr2 mRNA expression. Furthermore, TNF alpha and ADIPONECTIN significantly increased rarres2 and cmklr1 expression, respectively. In cultured bovine granulosa cells, human recombinant CHEMERIN (hRec, 200 ng/ml) reduced production of both progesterone and estradiol, cholesterol content, STAR abundance, CYP19A1 and HMGCR proteins, and the phosphorylation levels of MAPK3/MAPK1 in the presence or absence of FSH (10(-8) M) and IGF1 (10(-8) M). All of these effects were abolished by using an anti-CMKLR1 antibody. In bovine cumulus-oocyte complexes, the addition of hRec (200 ng/ml) in the maturation medium arrested most oocytes at the germinal vesicle stage, and this was associated with a decrease in MAPK3/1 phosphorylation in both oocytes and cumulus cells. Thus, in cultured bovine granulosa cells, hRec decreases steroidogenesis, cholesterol synthesis, and MAPK3/1 phosphorylation, probably through CMKLR1. Moreover, in cumulus-oocyte complexes, it blocked meiotic progression at the germinal vesicle stage and inhibited MAPK3/1 phosphorylation in both the oocytes and cumulus cells during in vitro maturation.
authors.affiliation: Unité Mixte de Recherches 7247 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours-Institut Français du Cheval et de l'Equitation, Nouzilly, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Reverchon
authors.affiliation: Unité Mixte de Recherches 7247 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours-Institut Français du Cheval et de l'Equitation, Nouzilly, France.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bertoldo
authors.affiliation: Unité Mixte de Recherches 7247 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours-Institut Français du Cheval et de l'Equitation, Nouzilly, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Ramé
authors.affiliation: Unité Mixte de Recherches 7247 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours-Institut Français du Cheval et de l'Equitation, Nouzilly, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Froment
authors.affiliation: Unité Mixte de Recherches 7247 Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique-Université de Tours-Institut Français du Cheval et de l'Equitation, Nouzilly, France jdupont@tours.fr.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dupont
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D002417:Cattle / Q000378:metabolism*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D007150:Immunohistochemistry / Q000662:veterinary; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008540:Meiosis / Q000502:physiology*; D008687:Metformin / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D010053:Ovary / Q000166:cytology / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D018925:Chemokines; D007328:Insulin; D019707:Receptors, Chemokine; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011374:Progesterone; D004958:Estradiol; D012313:RNA; D007334:Insulin-Like Growth Factor I; D008687:Metformin; D020928:Mitogen-Activated Protein Kinases
keywords: adipokine; cholesterol; follicle; granulosa; hormone action; oocyte maturation; ovary; reproduction; signaling pathways