title: NMR Metabolomics Show Evidence for Mitochondrial Oxidative Stress in a Mouse Model of Polycystic Ovary Syndrome.
abstract: Polycystic ovary syndrome (PCOS) is associated with metabolic and endocrine disorders in women of reproductive age. The etiology of PCOS is still unknown. Mice prenatally treated with glucocorticoids exhibit metabolic disturbances that are similar to those seen in women with PCOS. We used an untargeted nuclear magnetic resonance (NMR)-based metabolomics approach to understand the metabolic changes occurring in the plasma and kidney over time in female glucocorticoid-treated (GC-treated) mice. There are significant changes in plasma amino acid levels (valine, tyrosine, and proline) and their intermediates (2-hydroxybutyrate, 4-aminobutyrate, and taurine), whereas in kidneys, the TCA cycle metabolism (citrate, fumarate, and succinate) and the pentose phosphate (PP) pathway products (inosine and uracil) are significantly altered (p < 0.05) from 8 to 16 weeks of age. Levels of NADH, NAD(+), NAD(+)/NADH, and NADH redox in kidneys indicate increased mitochondrial oxidative stress from 8 to 16 weeks in GC-treated mice. These results indicate that altered metabolic substrates in the plasma and kidneys of treated mice are associated with altered amino acid metabolism, increased cytoplasmic PP, and increased mitochondrial activity, leading to a more oxidized state. This study identifies biomarkers associated with metabolic dysfunction in kidney mitochondria of a prenatal gluococorticoid-treated mouse model of PCOS that may be used as early predictive biomarkers of oxidative stress in the PCOS metabolic disorder in women.
authors.affiliation: †Department of Zoology, ‡Magnetic Resonance Facility at Madison, and §Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Ebru Selin
authors.initials: ES
authors.lastname: Selen
authors.affiliation: †Department of Zoology, ‡Magnetic Resonance Facility at Madison, and §Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Bolandnazar
authors.affiliation: †Department of Zoology, ‡Magnetic Resonance Facility at Madison, and §Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Marco
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: †Department of Zoology, ‡Magnetic Resonance Facility at Madison, and §Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Bütz
authors.affiliation: †Department of Zoology, ‡Magnetic Resonance Facility at Madison, and §Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Haviland
authors.affiliation: †Department of Zoology, ‡Magnetic Resonance Facility at Madison, and §Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Warren P
authors.initials: WP
authors.lastname: Porter
authors.affiliation: †Department of Zoology, ‡Magnetic Resonance Facility at Madison, and §Department of Animal Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Fariba M
authors.initials: FM
authors.lastname: Assadi-Porter
mesh_terms: D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002952:Citric Acid Cycle; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008659:Metabolic Diseases / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress; D010427:Pentose Phosphate Pathway; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D005938:Glucocorticoids; D006885:Hydroxybutyrates; D009243:NAD; C031570:2-hydroxybutyric acid
keywords: animal model; metabolomics; mitochondria; nuclear magnetic resonance (NMR); oxidative stress; polycystic ovary syndrome (PCOS)