Insulin-Like Growth Factor-I and Apoptosis As Determinants of Preimplantation Bovine Embryonic Development
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INSULIN-LIKE GROWTH FACTOR-I AND APOPTOSIS AS DETERMINANTS OF PREIMPLANTATION BOVINE EMBRYONIC DEVELOPMENT By FRANK DEAN JOUSAN A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2006 Copyright 2006 by Frank Dean Jousan This dissertation is dedicated to my parents and family. ACKNOWLEDGMENTS This dissertation would not have been possible without the dedication, guidance, and tireless support of Dr. Peter J. Hansen, chairman of my supervisory committee. I admire Dr. Hansen for his energy, enthusiasm, and passion that he has for science. Dr. Hansen works continuously toward the development and training of scientific minds while creating an enjoyable working environment. I am grateful for the opportunity that I had to work with Dr. Hansen and will always consider him to be an excellent mentor and great friend. Appreciation is also extended to the other members of my committee: Dr. William C. Buhi for his knowledge and support; Dr. Kenneth C. Drury for his interest and insight to my research; Dr. Karen Moore for her willingness to discuss science and dedication to providing such a high-quality embryology lecture and laboratory course; and Dr. Mats Troedsson for his willingness to allow opportunities for collaborations between our laboratories and his interesting, humorous conversations. I would like to extend my sincere thanks to the management and personnel at Central Packing Co. in Center Hill, FL, for providing the ovaries used in the majority of my experiments and to William Rembert for his assistance in collecting ovaries. Special thanks goes to the management and personnel at North Florida Holsteins (Bell, FL) and Brooksco Dairy (Quitman, GA) for allowing me to conduct field trials at their farms and providing me with assistance as needed. The field trial described in this dissertation would not have been possible without the tremendous amounts of time and labor provided by fellow graduate and iv undergraduate students in the laboratory, including Jeremy Block, Amber Brad, Dr. Amy Fisher-Brown, Moises Franco, Dr. Katherine Hendricks, Dr. Barbara Loureiro, Maria Padua, Dr. Luis Augusto de Castro e Paula, and Patrick Thompson. Additionally, I owe thanks to Dr. Fabíola Freitas de Paula-Lopes, Dr. Rocio Rivera, Dr. Zvi Roth, Dr. Paolete Soto, and Dr. Saban Tekin. Our laboratory is very diverse and I have enjoyed working with everyone, learning about his or her culture, and developing friendships with each person. I am grateful for the friendships and camaraderie of my fellow graduate students and faculty members (including Dr. Bill Thatcher, Dr. Dan Webb, and Dave Bray) in the Department of Animal Sciences. Additionally, I appreciate the assistance provided by Dr. Maarten Drost and Dr. Carlos Risco in the College of Veterinary Medicine. Participation in the Animal Molecular and Cellular Biology and Interdisciplinary Reproductive Biology program allowed me to interact on a social and scientific level with numerous students, faculty, and guests from around the world. Last but not least, I extend appreciation to my parents, Frank and Beverly Jousan Jr. Their never-ending love and unconditional moral and financial support have brought me to where I am today. They have always been an encouragement to my brother and me as we have pursued our goals in life. I would also like to thank my brother, Dr. Mark Jousan, for his encouragement and support. My family instilled in me the importance of God, family, and friends in life. For all of that and much more, I thank them. Even though I no longer live close to my family I still hold them close to me in my thoughts and prayers. To the rest of my family and friends in both the United States and around the world, I thank them for their friendship, thoughts, and prayers. v TABLE OF CONTENTS page ACKNOWLEDGMENTS ................................................................................................. iv LIST OF TABLES...............................................................................................................x LIST OF FIGURES ........................................................................................................... xi LIST OF ABBREVIATIONS.......................................................................................... xiii ABSTRACT.......................................................................................................................xv CHAPTER 1 INTRODUCTION ........................................................................................................1 2 LITERATURE REVIEW.............................................................................................6 Heat Stress and Fertility in Cattle.................................................................................6 Effects of Maternal Heat Stress on Fertility in Lactating Dairy Cows..................6 Mechanisms by Which Heat Stress Reduces Fertility...........................................7 Estrus behavior...............................................................................................7 Follicular development...................................................................................8 Reproductive tract ........................................................................................10 Oocyte competence and embryonic development........................................11 Developmental changes in resistance to heat shock.....................................14 Oxygen environment ....................................................................................14 Strategies to Increase Fertility during Heat Stress ..............................................16 Apoptosis and Heat Shock in Embryos ......................................................................18 Occurrence of Apoptosis in Bovine Embryos .....................................................18 Mechanism for Induction of Apoptosis by Heat Shock ......................................20 Developmental Changes in Occurrence and Consequences of Apoptosis during Embryonic Development......................................................................23 Actions of IGF-I to Modify Function of the Preimplantation Bovine Embryo..........24 Stimulation of Embryonic Development.............................................................25 Possible Mechanisms for Pro-Developmental Actions of IGF-I.........................28 Cytoprotective Actions of IGF-I .........................................................................30 Biology of Insulin-like Growth Factor-I.....................................................................31 IGF-I Ligand........................................................................................................31 Regulation of IGF-I Synthesis by ST and Insulin ...............................................32 Regulation of IGF-I Activity by Binding Proteins..............................................33 vi IGF-I Receptor.....................................................................................................34 Signal Transduction Pathways Mediated by the IGF-I Receptor........................37 Presence of IGF-I and Its Receptor in Reproductive Tissues..............................42 Follicle..........................................................................................................42 Corpus luteum ..............................................................................................43 Oviduct.........................................................................................................45 Uterus ...........................................................................................................45 Effects of bST in the Dairy Cow ................................................................................46 IGF-I Concentrations...........................................................................................46 Milk Yield ...........................................................................................................47 Reproduction .......................................................................................................49 Hypotheses for Dissertation........................................................................................54 3 INSULIN-LIKE GROWTH FACTOR-I AS A CYTOPROTECTIVE FACTOR FOR THE BOVINE PREIMPLANTATION EMBRYO EXPOSED TO HEAT SHOCK.......................................................................................................................56 Introduction.................................................................................................................56 Materials and Methods ...............................................................................................57 Materials..............................................................................................................57 In Vitro Production of Embryos..........................................................................59 TUNEL and Hoechst 33342 Labeling.................................................................60 Experiments.........................................................................................................61 Protective effect of IGF-I on heat-shock induced apoptosis........................61 Developmental competence of IGF-I-treated embryos subjected to heat shock.........................................................................................................62