title: A requirement for fatty acid oxidation in the hormone-induced meiotic maturation of mouse oocytes.
abstract: We have previously shown that fatty acid oxidation (FAO) is required for AMP-activated protein kinase (PRKA)-induced maturation in vitro. In the present study, we have further investigated the role of this metabolic pathway in hormone-induced meiotic maturation. Incorporating an assay with (3)H-palmitic acid as the substrate, we first examined the effect of PRKA activators on FAO levels. There was a significant stimulation of FAO in cumulus cell-enclosed oocytes (CEO) treated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and RSVA405. In denuded oocytes (DO), AICAR stimulated FAO only in the presence of carnitine, the molecule that facilitates fatty acyl CoA entry into the mitochondria. The carnitine palmitoyltransferase 1 activator C75 successfully stimulated FAO in CEO. All three of these activators trigger germinal vesicle breakdown. Meiotic resumption induced by follicle-stimulating hormone (FSH) or amphiregulin was completely inhibited by the FAO inhibitors etomoxir, mercaptoacetate, and malonyl CoA. Importantly, FAO was increased in CEO stimulated by FSH and epidermal growth factor, and this increase was blocked by FAO inhibitors. Moreover, compound C, a PRKA inhibitor, prevented the FSH-induced increase in FAO. Both carnitine and palmitic acid augmented hormonal induction of maturation. In a more physiological setting, etomoxir eliminated human chorionic gonadotropin (hCG)-induced maturation in follicle-enclosed oocytes. In addition, CEO and DO from hCG-treated mice displayed an etomoxir-sensitive increase in FAO, indicating that this pathway was stimulated during in vivo meiotic resumption. Taken together, our data indicate that hormone-induced maturation in mice requires a PRKA-dependent increase in FAO.
authors.affiliation: Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin 53233, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Valsangkar
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Downs
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000627:Aminophenols / Q000494:pharmacology; D066258:Amphiregulin; D000818:Animals; D054885:Cumulus Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D006835:Hydrazones / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008316:Malonyl Coenzyme A / Q000494:pharmacology; D008540:Meiosis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction; D012265:Ribonucleotides / Q000494:pharmacology; D013864:Thioglycolates / Q000494:pharmacology
chemical_list: C587848:AREG protein, human; D000214:Acyl Coenzyme A; D000627:Aminophenols; D066258:Amphiregulin; C587849:Areg protein, mouse; D066255:EGF Family of Proteins; D004852:Epoxy Compounds; D005227:Fatty Acids; D006023:Glycoproteins; D006835:Hydrazones; D036341:Intercellular Signaling Peptides and Proteins; C570843:RSVA405; D012265:Ribonucleotides; D013864:Thioglycolates; D000620:Aminoimidazole Carboxamide; D008316:Malonyl Coenzyme A; D004815:Epidermal Growth Factor; C017487:2-mercaptoacetate; D005640:Follicle Stimulating Hormone; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; C054207:etomoxir
keywords: AMPK; PRKA; fatty acid oxidation; meiotic resumption; oocyte maturation