title: Activation of cumulus cell SMAD2/3 and epidermal growth factor receptor pathways are involved in porcine oocyte-cumulus cell expansion and steroidogenesis.
abstract: Several lines of evidence suggest that in mice the activation of SMAD2/3 signaling by oocyte secreted factors, together with epidermal growth factor receptor (EGFR) activation, is essential to induce cumulus expansion. Here we show that inhibition of EGFR kinase in follicle stimulating hormone (FSH)-stimulated porcine oocyte-cumulus cell complex (OCCs) strongly decreases hyaluronan (HA) synthesis and its retention in the matrix, as well as progesterone synthesis. Although porcine cumulus cells undergo expansion independently of oocytes, we use biochemical and gene expression analyses to show that they do require activation of SMAD2/3 for optimal stimulation of HA synthesis and proteins involved in the organization of this polymer in the expanded matrix. Furthermore, FSH-induced progesterone synthesis by porcine cumulus cells was increased by blocking SMAD2/3 activation. In conclusion, these results support the hypothesis that an FSH-EGF autocrine loop is active in porcine OCCs, and provide the first evidence that the SMAD2/3 signaling pathway is induced by paracrine/autocrine factors in porcine cumulus cells and is involved in the control of both cumulus expansion and steroidogenesis.
authors.affiliation: Academy of Sciences of the Czech Republic, Institute of Animal Physiology and Genetics, Libechov, Czech Republic. nagyova@iapg.cas.cz
authors.forename: Eva
authors.initials: E
authors.lastname: Nagyova
authors.forename: Antonella
authors.initials: A
authors.lastname: Camaioni
authors.forename: Sona
authors.initials: S
authors.lastname: Scsukova
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Mlynarcikova
authors.forename: Radek
authors.initials: R
authors.lastname: Prochazka
authors.forename: Lucie
authors.initials: L
authors.lastname: Nemcova
authors.forename: Antonietta
authors.initials: A
authors.lastname: Salustri
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002097:C-Reactive Protein / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism; D054885:Cumulus Cells / Q000378:metabolism*; D004149:Dioxoles / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007546:Isoquinolines / Q000494:pharmacology*; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D009865:Oocytes / Q000201:enzymology* / Q000502:physiology; D011374:Progesterone / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology; D000683:Serum Amyloid P-Component / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013552:Swine; D020032:Tyrphostins / Q000494:pharmacology; D000099153:Pentraxins
chemical_list: D001549:Benzamides; D002097:C-Reactive Protein; D015815:Cell Adhesion Molecules; D004149:Dioxoles; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D005640:Follicle Stimulating Hormone; D014453:Glucuronosyltransferase; D006820:Hyaluronic Acid; D007546:Isoquinolines; D011374:Progesterone; D011725:Pyridines; D011758:Pyrroles; D011799:Quinazolines; D000683:Serum Amyloid P-Component; D051899:Smad2 Protein; D051900:Smad3 Protein; D020032:Tyrphostins; D000099153:Pentraxins; C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; C508504:6,7-dimethyl-2-(2E)-3-(1-methyl-2-phenyl-1H-pyrrolo(2,3-b)pyridin-3-yl-prop-2-enoyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride; C101044:RTKI cpd