Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2020 Impact of polycystic ovary syndrome on methyl group metabolism Amanda Bries Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Recommended Citation Bries, Amanda, "Impact of polycystic ovary syndrome on methyl group metabolism" (2020). Graduate Theses and Dissertations. 18283. https://lib.dr.iastate.edu/etd/18283 This Thesis is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Impact of polycystic ovary syndrome on methyl group metabolism by Amanda Elizabeth Bries A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Nutritional Sciences Program of Study Committee: Kevin Schalinske, Major Professor Aileen Keating Matthew Rowling Manju Reddy Elizabeth McNeill Rachel Derscheid The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this dissertation. The Graduate College will ensure this dissertation is globally accessible and will not permit alterations after a degree is conferred. Iowa State University Ames, Iowa 2020 Copyright © Amanda Elizabeth Bries, 2020. All rights reserved. ii TABLE OF CONTENTS Page LIST OF FIGURES ....................................................................................................................... iv LIST OF TABLES ...........................................................................................................................v NOMENCLATURE ...................................................................................................................... vi ACKNOWLEDGMENTS ............................................................................................................. xi ABSTRACT ................................................................................................................................. xiii CHAPTER 1. GENERAL INTRODUCTION ................................................................................1 Introduction ............................................................................................................................... 1 Dissertation Organization .......................................................................................................... 2 References ................................................................................................................................. 3 CHAPTER 2. LITERATURE REVIEW .........................................................................................5 Polycystic Ovary Syndrome ...................................................................................................... 5 Hypothalamic Pituitary Ovarian Axis .................................................................................. 5 Pathogenesis ......................................................................................................................... 8 Diagnostic Criteria ............................................................................................................. 10 Lifestyle Modifications and Therapeutic Treatments ........................................................ 11 Animal Models of PCOS ......................................................................................................... 14 Chemically-induced............................................................................................................ 15 Genetic Models................................................................................................................... 17 Methyl Group Metabolism ...................................................................................................... 19 Nutrients and Methyl Group Metabolism .......................................................................... 21 Estrogen and Methyl Group Metabolism ........................................................................... 23 PCOS and Methyl Group Metabolism ............................................................................... 24 Hyperhomocysteinemia ........................................................................................................... 25 Pathogenesis of Hyperhomocysteinemia ............................................................................ 31 Association with PCOS ...................................................................................................... 32 Nutrition, Homocysteine, and PCOS ................................................................................. 34 Summary .................................................................................................................................. 38 References ............................................................................................................................... 38 CHAPTER 3. LETROZOLE-INDUCED POLYCYSTIC OVARY SYNDROME ATTENUATES CYSTHATIONINE β-SYNTHASE MRNA AND PROTEIN ABUNDANCE IN THE OVARIES OF FEMALE SPRAGUE DAWLEY RATS ................................................55 Abstract .................................................................................................................................... 55 Introduction ............................................................................................................................. 56 Materials and Methods ............................................................................................................ 58 Results ..................................................................................................................................... 62 Discussion ................................................................................................................................ 65 iii Acknowledgments ................................................................................................................... 70 References ............................................................................................................................... 70 Tables and Figures ................................................................................................................... 75 CHAPTER 4. POLYCYSTIC OVARY SYNDROME MODULATES BETAINE HOMOCYSTEINE S-METHYLTRANSFERASE IN 8 WEEK OLD FEMALE LETHAL YELLOW AGOUTI MICE ...........................................................................................................82 Abstract .................................................................................................................................... 82 Introduction ............................................................................................................................. 83 Materials and Methods ............................................................................................................ 84 Results ..................................................................................................................................... 88 Discussion ................................................................................................................................ 91 Conclusion ............................................................................................................................... 96 References ............................................................................................................................... 96 CHAPTER 5. GENERAL CONCLUSIONS ...............................................................................107 Overall summary and conclusions ......................................................................................... 107 APPENDIX A. WHOLE EGG CONSUMPTION INCREASES GENE EXPRESSION WITHIN THE GLUTATHIONE PATHWAY IN THE LIVER OF ZUCKER DIABETIC FATTY RATS .............................................................................................................................112 APPENDIX B. LARGE AND SMALL RNA SEQUENCING REVEALS OXIDATIVE- REDUCTION PATHWAYS ARE MODIFID BY SHORT-TERM WHOLE EGG CONSUMPTION. ........................................................................................................................171 APPENDIX C. ACUTE SERUM AND NON-TRANSFERRIN BOUND IRON AND GASTROINTESTINAL SYMPTOMS WITH 3 WEEK CONSUMPTION ARE LOWER WITH IRON-ENRICHED ASPERGILLUS ORYZAE COMPARED TO FERROUS SULFATE ....................................................................................................................................200 APPENDIX D. IRON SUPPLEMENTATION CONFERS PROTECTION AGAINST DISEASE SEVERITY IN DEXTRAN SODIUM SULFATE (DSS)-INDUCED COLITIS IN RATS ...........................................................................................................................................225 iv LIST OF FIGURES Page Figure 2-1. Hypothalamic-pituitary-gonadal axis. ......................................................................... 6 Figure 2-2. Two-cell theory of theca and granulosa cell production of androgen and estradiol under healthy conditions. ............................................................................. 7 Figure 2-3. Therapeutic strategies for PCOS management.........................................................