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Novel Approaches to Positively Impact the Early Life Physiology, Endocrinology, and Productivity of Bulls

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Novel Approaches to Positively Impact the Early Life Physiology, Endocrinology, and Productivity of Bulls Novel Approaches to Positively Impact the Early Life Physiology, Endocrinology, and Productivity of Bulls DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Bo R. Harstine, M.S. Graduate Program in Animal Sciences The Ohio State University 2016 Dissertation Committee: Dr. Michael L. Day, Advisor Mel DeJarnette Dr. Christopher Premanandan Dr. Gustavo Schuenemann Dr. Joseph Ottobre Copyrighted by Bo Randall Harstine 2016 ABSTRACT Changes to sire selection, such as the utilization of genomic evaluations, have created a desire to collect semen from superior sires as early as possible. Therefore, a series of experiments was performed in order to determine whether a novel exogenous FSH treatment hastened puberty and positively impacted postpubertal semen production in bulls. In the first experiment, angus-cross bulls received either 30 mg NIH-FSH-P1 in a 2% hyaluronic acid solution (FSH-HA, n =11) or saline (control, n = 11) every 3.5 days from 59 to 167.5 days of age. Blood was collected every 7 days to determine testosterone concentrations and at 59, 84, 94, 130, and 169 days of age to determine activin A concentrations. FSH concentrations were determined from blood collected preceding treatment every 3.5 days, as well as during three intensive collections commencing at 66, 108, and 157 days of age. Castration was performed at 170 days of age to examine testis weight, volume, diameter of seminiferous tubules, and the number of Sertoli cells per tubule cross section. Concentrations of FSH did not differ from 59 to 91 days of age, but became greater (P < 0.05) in FSH-HA than control bulls from 94 to 167.5 days. For each intensive sampling, FSH concentration was elevated (P < 0.05) in FSH-HA bulls for at least 18 hours post-injection at all ages examined. Activin A concentrations were greater ii in FSH-HA than control bulls at 84 and 94 days. Testosterone concentrations, testis weight, testis volume, and seminiferous tubule diameter did not differ between treatments, but FSH-HA bulls had greater (P < 0.05) numbers of Sertoli cells per tubule cross section (45.2 ± 1.4 vs. 41.7 ± 0.9 cells). In a second experiment, Holstein bulls were utilized to determine the FSH-HA treatment's effect on puberty attainment and mature sperm production. Bulls received either the FSH-HA treatment (FSH-HA, n = 17) or saline (n = 12) every 3.5 days from 62 to 170.5 days of age. Concentrations of FSH did not differ between treatments from 62 to 93.5 days of age, but became greater (P < 0.05) in FSH-HA bulls from 97 to 170.5 days of age. Activin A concentrations measured at 62, 86.5, 107.5, 139, and 170.5 days were greater (P < 0.05) in FSH-HA than control bulls at 86.5 and 107.5 days. FSH-HA bulls reached puberty (ability to produce 50 x 106 cells, 10% motility) sooner (P < 0.05) than control bulls (278 ± 7.7 vs. 303 ± 9.1 days), but there was no differences in mature sperm production measured from 571 to 627 days of age. Together, these experiments highlight the efficacy of a novel FSH-HA treatment to hasten puberty. We propose that FSH-HA treatment positively effects the hypothalamo-pituitary-gonadal axis of bulls by stimulating the feedback loop involving activin A and FSH production as evidence by increased Sertoli cells. Impacts of this research are important not only to AI organizations, but also for cattle producers who AI their cows, and for consumers who rely on efficient food production. iii ACKNOWLEDGEMENTS Attaining a Ph.D. has been a humbling experience, but reflecting on my work over the last three years makes me realize how fortunate I am. I have made many new personal and professional connections, been given the chance to study and work abroad, and have learned a lot about what drives and motivates me. While few would argue that self-reliance was critical to my success—especially in the later stages of this degree—I must give credit to the many people who helped me along the way. To Mike Day, thank you for giving me a firm understanding of science and research. There is no doubt that I'll be using skills you taught me during my future endeavors and careers. Thanks to your family for always being welcoming. I pride myself on being your last graduate student (at Ohio State, at least), and please know that your well-respected career has acted as a springboard for myself as well as your other students. Thank you to my committee members who provided expertise and insight throughout the process. Some, such as Mel DeJarnette and Chris Premanandan, have been honing my research skills for over five years. In addition, I appreciate the guidance and suggestions from Gustavo Schuenemann and Joe Ottobre. Many of these projects would not have been possible without colleagues at Select Sires. I associated with many of the personnel at SS even before graduate school, and I'm iv so excited to begin working alongside some of the same people after completing this degree. Thanks to Clif and Mel for seeing me as a person worth mentoring. Thanks to the calf-campus, collection, and laboratory processing employees for letting me make your work more difficult. Thank you to the OSU Beef Center crew for helping me with these projects. Marty and Gregg, thank you for advice and for the care of the animals over the years. Although I'm finishing graduate school as the sole member of the lab, I have to thank past lab mates for their friendship and the knowledge they provided. Leandro, Fernanda, Matt, Martin, thank you for being friends and teachers. It is exciting that we may all work closely together in the future. It's comforting to know that we've established work and personal friendships that will last for a long time. To my family, thank you for being a constant source of support. Mom and Dad, I'm so grateful for the upbringing you gave Tyler, Colton, and I. You've instilled an incredible sense of determination and decency in all of us. The older I get, the more I appreciate growing up on a dairy farm and the lessons it taught me. Not many of my peers are blessed with such experiences. Katherine, thank you for your love and support! If you faint in the day of adversity, your strength is small. Proverbs 24:10 v Vita February 7, 1989................................ Born – Dundee, Ohio 2011................................................... B.A. Cellular and Molecular Biology, Washington & Jefferson College, Washington, Pennsylvania 2013................................................... M.S. Animal Science, The Ohio State University, Columbus, Ohio 2013 to present....................................OSU-Select Sires-C.E. Marshall Graduate Research Associate, The Ohio State University, Columbus, Ohio Field of Study Major Field: Animal Sciences Reproductive Physiology and Endocrinology vi Table of Contents Abstract ............................................................................................................................... ii Acknowledgments.............................................................................................................. iv Vita ..................................................................................................................................... vi List of Tables ...................................................................................................................... x List of Figures .................................................................................................................... xi Chapter 1: Introduction and Statement of the Problem ..................................................... 1 Introduction ............................................................................................................. 1 Statement of the Problem ........................................................................................ 3 Chapter 2. Review of the Literature .................................................................................... 5 2.1. The Events Preceding Puberty in the Bull ....................................................... 5 2.1.1. Putting Bull Puberty in Context ........................................................ 5 2.1.2. Initiation of GnRH Production and Activation of the Hypothalamo- Pituitary-Gonadal Axis ....................................................................................................... 7 2.1.3. Initiation of LH Pulsatility and Testosterone Production ............... 10 vii 2.1.4. Development of the FSH, Activin, Inhibin, and Follistatin Pathways ........................................................................................................................................... 14 2.1.5. Cellular and Structural Changes of the Gonad Preceding Puberty and Spermatogenesis ......................................................................................................... 24 2.2. Overview of Testicular Physiology and Endocrinology in Mature Bulls ...... 31 2.2.1. GnRH, LH, Testosterone, and Leydig Cells ................................... 31 2.2.2. FSH, Sertoli Cells, and Spermatogenesis ....................................... 34 2.2.3. Inhibin, Activin, and Follistatin ...................................................... 37 2.3. Previous Methods to Hasten Puberty in Bulls ............................................... 39 2.3.1. Direct Endocrine Manipulations to Advance Puberty .................... 40 2.3.2. Dietary Manipulations to Advance Puberty .................................... 46 2.4. The Selection
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