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Direct Effects of Heat Stress During Meiotic Maturation on Bovine Oocyte and Cumulus RNA

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Direct Effects of Heat Stress During Meiotic Maturation on Bovine Oocyte and Cumulus RNA University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 12-2009 Direct Effects of Heat Stress During Meiotic Maturation on Bovine Oocyte and Cumulus RNA Rebecca R. Payton University of Tennessee - Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Animal Sciences Commons Recommended Citation Payton, Rebecca R., "Direct Effects of Heat Stress During Meiotic Maturation on Bovine Oocyte and Cumulus RNA. " PhD diss., University of Tennessee, 2009. https://trace.tennessee.edu/utk_graddiss/628 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Rebecca R. Payton entitled "Direct Effects of Heat Stress During Meiotic Maturation on Bovine Oocyte and Cumulus RNA." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Doctor of Philosophy, with a major in Animal Science. J. Lannett Edwards, Major Professor We have read this dissertation and recommend its acceptance: Cheryl Kojima, Arnold Saxton, F. Neal Schrick, Neal Stewart Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) To the Graduate Council: I am submitting herewith a dissertation written by Rebecca Ruth Payton entitled ―Direct Effects of Heat Stress During Meiotic Maturation on Bovine Oocyte and Cumulus RNA.‖ I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Animal Science. J. Lannett Edwards ____________________________________ Major Professor We have read this dissertation and recommend its acceptance: Cheryl Kojima ____________________________________ Arnold Saxton ____________________________________ F. Neal Schrick ____________________________________ Neal Stewart ____________________________________ Acceptance for the Council: Carolyn R. Hodges _____________________________________ Vice Provost and Dean of the Graduate School (Original signatures are on file with official student records.) DIRECT EFFECTS OF HEAT STRESS DURING MEIOTIC MATURATION ON BOVINE OOCYTE AND CUMULUS RNA A Dissertation Presented for the Doctor of Philosophy Degree The University of Tennessee, Knoxville Rebecca Ruth Payton December 2009 DEDICATION This dissertation is dedicated to my best friend and husband, Jason, whose patience and understanding have made the valleys along this journey bearable. ii ACKNOWLEDGMENTS I feel it necessary to first thank God, without whom I would not have had the endurance to finish this seemingly never-ending process. His grace and mercy never cease to awe me. I am also greatly indebted to my committee members. Dr. Kojima, thank you for your insight and kind words over the years. Dr. Stewart, I appreciate your unique perspective on this research and your willingness to have me in your lab to learn the ―RNA ropes.‖ Dr. Saxton, there are not adequate words to describe what a blessing you have been in my graduate career. I am so glad I finally found out what your favorite cookie is so I can offer some small token of appreciation (even though it has been much too infrequent). Dr. Schrick, thank you for always being a voice of reason and continually reminding me to keep coming ―back to the cow.‖ Dr. Edwards, I SO value your honesty, persistence, and belief in me, despite having been frustrated to tears at times. You taught me the invaluable skill of teaching myself. There is no way I could have done any of this without you and your continuing support (it keeps going and going…). There are so many people that have made lab life so much fun. Janelle Lawrence, Melody Malone, TJ Wilson, Fernando Scenna, Gretchen Schrock, Amanda Ward, Jessy Harris, Courtney Crabtree, Erin Bartley, Nancy Rohrbach, Lisa Amelse, Tan Tan Sun, Estanislao Peixoto, Brooke Middlebrooks, and all the other ―Schricklets‖ and undergraduate workers over the years. I am particularly grateful for Louisa Rispoli; you are the one who really brought molecular biology to the lab and without your input, Dr. Edwards and I might still be arguing about how long RNA can be stored at -80ºC in lysis buffer. You have also been an amazing friend and gave me the gift of homemade sushi. Dr. Mathew, thank you for your support, both iii emotionally and financially, of graduate education. Mark and Roger, thank you for all the fun conversations around JARTU and for silencing the alarms always going off at inopportune times (and there never has been a fire…). This entire process would not have been possible without the unending love and support of my family and friends. Mama, I have no doubt that you would walk to the ends of the earth on your hands and knees if you thought it would help. Thank you for always taking time, no matter how busy you were, to spend a few minutes with me just to see how I was doing. You are an amazing mom and an even more amazing person. Daddy, thanks for making sure we appreciated the beauty of nature and the value of physical labor— homegrown food and fresh fish really do taste better. Granny, your strength in all situations is an inspiration. Thank you for the many calls, cards, and words of encouragement. To all my church family—so many of you have prayed for this day. You have no idea how much I covet your petitions on my behalf. Most importantly, I must thank the man who has been my sponsor, monetarily and emotionally, for over 8 years now. Jason, I hope you think it has been worth it. I do not know what the future holds but God has taken care of us so far (because we are more important than the birds!). iv ABSTRACT Heat-induced reductions in developmental competence after direct exposure of oocytes to 41ºC have been coincident with reduced protein synthesis. Since heat stress perturbs RNA integrity and polyadenylation in somatic cells, it was hypothesized that heat stress during meiotic maturation may alter RNA within oocytes and/or their surrounding cumulus to account for some of the reductions in development. Initial efforts utilized microcapillary electrophoresis to examine oocyte and cumulus RNA without heat stress as a first step toward transcriptome profile analysis. Size distribution of RNA, rRNA ratio, and other related endpoints differed for oocyte RNA compared to cumulus, and were conserved across other mammalian species. Size distribution of polyadenylated RNA after amplification was similar for oocytes and cumulus. Effects of heat stress on total and polyadenylated RNA, RNA size distribution, and individual transcripts important for meiotic maturation and response to heat stress were examined in oocytes and cumulus during maturation, and resultant embryos after fertilization. There was no impact of heat stress during the first 12 h of maturation to alter size distribution of RNA, rRNA ratio, and other endpoints in oocytes or cumulus. Heat stress perturbed the abundance of polyadenylated RNA in oocytes in one study. Abundance of eight examined transcripts was not altered after exposure to elevated temperature, suggesting that the impact of heat stress on oocyte RNA, if any, was subtle. Consequences of elevated temperature exposure during maturation on transcriptomes of oocytes and their surrounding cumulus vestment were investigated using microarray technology. Thousands of transcripts changed in oocytes and surrounding cumulus over meiotic maturation, some in a stage-specific and amplification-dependent manner. Culture at elevated temperature v for the first 12 h of meiotic maturation impacted a small proportion of transcripts in matured oocytes and cumulus at 24 h. Alterations suggested perturbations in oocyte mitochondrial function, and intracellular signaling and extracellular matrix production in cumulus. Heat- induced alterations in oocyte mitochondria and cumulus expansion are supported by existing literature. The findings discussed here are informative of heat-induced molecular alterations in oocytes and cumulus and may prove useful for development of strategies to mitigate negative impacts of heat stress on fertility. vi TABLE OF CONTENTS Page LIST OF TABLES ........................................................................................................................ x LIST OF FIGURES .................................................................................................................... xii CHAPTER 1:GENERAL INTRODUCTION ............................................................................ 1 CHAPTER 2:LITERATURE REVIEW .................................................................................... 7 THE LIFE OF AN OOCYTE ...................................................................................................... 7 Oogenesis and Folliculogenesis ............................................................................................. 7 Growth Phase.......................................................................................................................... 8
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