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Maternal Nutritional Plane and Endogenous Retroviral Gene

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Maternal Nutritional Plane and Endogenous Retroviral Gene MATERNAL NUTRITIONAL PLANE AND ENDOGENOUS RETROVIRAL GENE ELEMENTS, PREGNANCY HORMONES, AND PLACENTAL VASCULARITY AND ANGIOGENIC FACTORS DURING THE ESTABLISHMENT OF PREGNANCY IN BEEF CATTLE A Dissertation Submitted to the Graduate Faculty of the North Dakota State University of Agriculture and Applied Science By Kyle James McLean In Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY Major Department: Animal Sciences Option: Nutritional Physiology September 2016 Fargo, North Dakota North Dakota State University Graduate School Title Maternal Nutritional Plane and Endogenous Retroviral Gene Elements, Pregnancy Hormones, and Placental Vascularity and Angiogenic Factors during the Establishment of Pregnancy in Beef Cattle By Kyle James McLean The Supervisory Committee certifies that this disquisition complies with North Dakota State University’s regulations and meets the accepted standards for the degree of DOCTOR OF PHILOSOPHY SUPERVISORY COMMITTEE: Dr. Joel Caton Chair Dr. Lawrence Reynolds Dr. Carl Dahlen Dr. Pawel Borowicz Dr. Eugene Berry Approved: November 1, 2016 Dr. Gregory Lardy Date Department Chair ABSTRACT In order to meet the projected food demands by 2050, animal agriculture must increase production of animal products on the same or decreased land area through increased efficiency. Early gestation is one area to increase efficiency in beef production in a twofold manner 1) by increasing the number of calves born due to decreased early embryonic loss and 2) by minimizing detrimental effects due to fetal programming which may decrease offspring growth or reproductive efficiency. Both of which will result in more pounds of beef produced by the same number of cows. Recently, endogenous retroviral elements (ERV), which make up a significant portion of mammalian genomes, have been implicated in vital steps during placentation. The placenta is the source of nutrient, gas, and waste exchange between maternal and fetal circulation which is necessary to support fetal growth. Maternal nutrition influences fetal growth and placental development. Therefore, we hypothesized that ERV envelope genes, syncytin-Rum1 and BERV-K1 , as well as pregnancy specific hormones, PSP-B, and IFN-τ will be differentially expressed during critical time points of early pregnancy and maternal nutrition restriction will alter mRNA expression at critical time points. We developed a technique to ovariohysterectomized beef heifers which provides a large animal model to acquire utero- placental tissues. In year 1, we established basal expression patterns for syncytin-Rum1 and BERV-K1 , PSP-B, and IFN-τ within utero-placental tissues during the first 50 d of gestation. In year 2, we determined the effects of 40% global nutrient restriction on the mRNA expression of syncytin-Rum1 and BERV-K1 , PSP-B, and IFN-τ on d 16, 34, and 50 of gestation in utero- placental tissues. These data provide novel evidence of differential expression of endogenous retroviruses ( syncytin-Rum1 and BERV-K1), PSP-B, and IFN-τ during early gestation but 40% maternal nutrient restriction had little influence of mRNA expression. However, further work iii needs to be completed to elucidate functions, mechanisms, and interactions of these genes during early gestation and their importance to the successful establishment of pregnancy. iv ACKNOWLEDGEMENTS I would like to start off by thanking my committee members, Dr. Caton, Dr. Reynolds, Dr. Dahlen, Dr. Borowicz, and Dr. Berry, for allowing my imagination to run wild at times but also making these ideas a reality. They were not only supportive and instrumental in the completion of this project and my degree but also extremely flexible and willing to work with me. I would also like to thank Dr. Walden and Dr. Neville for the part they played in the development of the hysterectomy technique. Their support and belief in me and this group were vital to the successful development of this technique. This section would not be complete without an immense thank you going out to the barn crew at the Animal Nutrition and Physiology Center who spent many hours feeding and taking care of these animals before, during, and after these research projects. As well as, all of the staff members at Hultz Hall, in the offices and labs, the animal science graduate students, and the members at the other NDSU barns who were always will to help when they could. A special thanks needs to go to Jim Kirsch, Sheri Dorsam, and Marsha Kapphahn who were always available to answer questions when I was over my head and/or on a short timeline. Last but certainly not least I would like to special send a thank you to Matthew Crouse. While I gave him a hard time about almost everything, his hard work and wiliness to come in at odd hours to help made this project much, much more enjoyable. Finally, I owe all of my success to the support and guidance of Dr. Caton. He pushed the limits of my knowledge but always set me up to success. I am sure that I am forgetting several people but for those I have mentioned and those who I missed I cannot begin to express my gratitude for all that you have done to help me through my time here at NDSU. I will always remember the times spent here in Fargo and couldn’t have asked for a better opportunity. v DEDICATION I would like to dedicate this dissertation to my mom, dad, and little brother who have supported me through many, many years of school. I would not be who I am today without them. I will never be able to truly express my gratitude for all they have done. I would also like to dedicate this to my fiancée, Amanda, she was always there to listen and could relate and understand what I was actually complaining about. vi TABLE OF CONTENTS ABSTRACT ................................................................................................................................... iii ACKNOWLEDGEMENTS ............................................................................................................ v DEDICATION ............................................................................................................................... vi LIST OF TABLES ......................................................................................................................... xi LIST OF FIGURES ...................................................................................................................... xii LIST OF ABBREVIATIONS ...................................................................................................... xiv CHAPTER 1. INTRODUCTION ................................................................................................... 1 CHAPTER 2. LITERATURE REVIEW ........................................................................................ 4 2.1. Introduction .......................................................................................................................... 4 2.2. Retroviruses .......................................................................................................................... 6 2.2.1. Syncytia Formation ....................................................................................................... 6 2.2.2. Bovine Retroviral Elements .......................................................................................... 7 2.2.3. Syncytin in Other Mammals .......................................................................................... 8 2.2.4. Endogenous Jaagsiekte Sheep Retrovirus ..................................................................... 9 2.3. Pregnancy Establishment ................................................................................................... 10 2.3.1. Interferon-Tau.............................................................................................................. 10 2.3.2. Maternal Recognition of Pregnancy ............................................................................ 11 2.3.3. Pregnancy Specific Protein-B ...................................................................................... 13 2.3.4. Roles of Other Hormones ............................................................................................ 15 2.3.5. Changes in Uterine Tissues ......................................................................................... 17 2.4. Fetal Development ............................................................................................................. 18 2.4.1. Pre-Implantation .......................................................................................................... 18 2.4.2. Apposition, Implantation, and Adhesion ..................................................................... 19 2.4.3. Angiogenesis and Placental Vascularization ............................................................... 20 vii 2.5. Developmental Programming ............................................................................................ 21 2.5.1. Nutritional Influences on Fetal Growth, Development and Survival .......................... 21 2.5.2. Bovine.......................................................................................................................... 22 2.5.3. Ovine ........................................................................................................................... 24 2.5.4. Nutritional Influences on Placental Development ....................................................... 25 2.6. Summary and Conclusions ................................................................................................
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