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A Study of the Impact of Environmental Chemicals and Micronutrients on Pubertal Development in a Mexican Population

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A Study of the Impact of Environmental Chemicals and Micronutrients on Pubertal Development in a Mexican Population A Study of the Impact of Environmental Chemicals and Micronutrients on Pubertal Development in A Mexican Population by Yun Liu A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Nutritional Sciences) in the University of Michigan 2017 Doctoral Committee: Professor Karen E. Peterson, Chair Assistant Professor Andrew Jones Professor Angeles E. Martínez-Mier, Indiana University Associate Professor Brisa N. Sánchez Yun Liu [email protected] ORCID iD: 0000-0002-2979-9552 Copyright © Yun Liu 2017 DEDICATION This dissertation is dedicated to my parents, Hui Li and Xiumin Liu, for all of their love and support ii ACKNOWLEDGEMENTS First, I would like to express my deepest gratitude to my adviser and committee chair, Dr. Karen Peterson, for her mentorship in both academia and life and for all the opportunities that she has provided over the course of my doctoral training. I am very grateful for all the support that she has given me to pursue all my “crazy” but “creative” research ideas and projects, even when these ideas took longer than expected to implement. I am also very thankful that I have been able to shadow her at grant planning meetings and research meetings, participate in her teaching, and work on invited research articles and book chapters with her. After five years working with her, I have grown professionally and I have become more confident to pursue a career in academia. I would also like to thank all my committee members. Dr. Angeles Martínez-Mier offered me the training in fluoride measurement and analysis in her lab. I have learnt a lot about fluoride metabolism from her and very much enjoyed my stay at Indiana University with her colleagues and lab staff. I am very grateful for her excellent guidance by sharing her extensive knowledge of fluoride (pretty much everything about fluoride), and her rational thinking. Dr. Brisa Sánchez provided guidance with developing and applying statistical analysis in all my dissertation research projects, and I am very thankful for all the time she spent with me going over my analysis plans and reviewing all my manuscripts. Dr. Andrew Jones gave particularly excellent suggestions on iii how to pursue the research questions and provided valuable recommendations on establishing and refining analysis strategies. All of my committee members have provided me with extensive knowledge, critical and creative thinking of research questions, and enthusiasm for science, all of which will be a great asset to my academic career in future. Additionally, I would like to give my special thank you to all my collaborators, who played crucial roles in my dissertation research. My dissertation research would not have been possible without the commitment and dedication of the great ELEMENT fieldwork team, Dr. Mara Tellez Rojo, Ana Benito, and Luis Fernando Bautista Arredondo, who were in charge of the fieldwork conducted in Mexico. Dr. Adrienne Ettinger and Dr. Alejandra Cantoral provided valuable suggestions on my micronutrient projects by sharing the methods they used and their extensive knowledge of nutritional epidemiology. I would also like to extend my gratitude to my fellow graduate students and lab members. Dr. Deena Thomas, who was a fellow doctoral student, provided sample measurements and guidance and assistance with life as a graduate student. Nicole Kruise, Christine Buckley and Prithvi Chandrappa at Indiana University analyzed most of the fluoride samples and without their hard work, this work also would not have moved forward. Finally, I would like to thank Dr. Kirsten Herold at the SPH Writing Lab at the University of Michigan for her very last minute assistance with this dissertation. I also could not have done this work without the support of Dr. Zhenzhen Zhang, Lu Tang, and Dr. Ling Zhou, who were generous with sharing their expertise in biostatistics by helping with iv extracting datasets, even on a very short notice, and providing their suggestions on selection of regression models. Many thanks to my friends and peers at the department of Environmental Health Sciences and Nutritional Sciences. I would also like to thank all the staff at Environmental Health Sciences and Nutritional Sciences for all the help they provided through my doctoral training. Finally, I would like to acknowledge the participants of the ELEMENT cohorts in Mexico City. My dissertation research would not be possible without their dedication to scientific research. Also, I am grateful for NIEHS (R01ES021446), Lifecourse Exposures and Diet: Epigenetics, Maturation and Metabolic Syndrome (1P01ES022844-01/RD 83543601), that supported me over the course of my doctoral training at University of Michigan. v Table of Contents Dedication………………………………………………………………………………………...ii Acknowledgements……………………………………………………………….......................iii List of Figures ............................................................................................................................viii List of Tables ................................................................................................................................ix List of Acronyms ..........................................................................................................................xi Abstract ......................................................................................................................................xiii CHAPTER 1 Introduction ...........................................................................................................1 1.1. Secular trends in pubertal development....................................................................................1 1.2. Long-term health consequences of early puberty.....................................................................2 1.3. Environmental influences on early puberty..............................................................................4 1.4. Regulation of pubertal development.........................................................................................6 1.5. Study population........................................................................................................................9 1.6. Dissertation overview .............................................................................................................11 CHAPTER 2 Prenatal and Peripubertal Fluoride in Relation to Sexual Maturation and Its Related Serum Hormones in Mexican Children...................................................................... 16 2.1. Abstract ..................................................................................................................................16 2.2. Introduction ............................................................................................................................18 vi 2.3. Methods ..................................................................................................................................21 2.4. Results.....................................................................................................................................26 2.5. Discussion ..............................................................................................................................28 2.6. Conclusions.............................................................................................................................30 CHAPTER 3 Maternal Intake of Micronutrients during Pregnancy in Relation to Sexual Maturity in Mexican Children....................................................................................................42 3.1. Abstract ..................................................................................................................................42 3.2. Introduction ............................................................................................................................44 3.3. Methods ..................................................................................................................................47 3.4. Results.....................................................................................................................................51 3.5. Discussion ..............................................................................................................................52 3.6. Conclusions.............................................................................................................................55 CHAPTER 4 Life Stage Lead Exposures and Development and Tempo of Puberty……....63 4.1. Abstract ..................................................................................................................................63 4.2. Introduction ............................................................................................................................65 4.3. Methods ..................................................................................................................................67 4.4. Results.....................................................................................................................................73 4.5. Discussion ..............................................................................................................................76 4.6. Conclusions.............................................................................................................................79 CHAPTER 5 Conclusions............................................................................................................86
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