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Alterations to Maternal Behavior and Brain by Exogenous Estrogen Exposure

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Alterations to Maternal Behavior and Brain by Exogenous Estrogen Exposure University of Massachusetts Amherst ScholarWorks@UMass Amherst Doctoral Dissertations Dissertations and Theses November 2016 Alterations to Maternal Behavior and Brain by Exogenous Estrogen Exposure Mary Catanese University of Massachusetts Amherst Follow this and additional works at: https://scholarworks.umass.edu/dissertations_2 Part of the Neuroscience and Neurobiology Commons Recommended Citation Catanese, Mary, "Alterations to Maternal Behavior and Brain by Exogenous Estrogen Exposure" (2016). Doctoral Dissertations. 733. https://doi.org/10.7275/9054076.0 https://scholarworks.umass.edu/dissertations_2/733 This Open Access Dissertation is brought to you for free and open access by the Dissertations and Theses at ScholarWorks@UMass Amherst. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of ScholarWorks@UMass Amherst. For more information, please contact [email protected]. ALTERATIONS TO MATERNAL BEHAVIOR AND BRAIN BY EXOGENOUS ESTROGEN EXPOSURE A Dissertation Presented by MARY CATANESE Submitted to the Graduate School oF the University oF Massachusetts Amherst in partial FulFillment oF the requirements For the degree oF DOCTOR OF PHILOSOPHY September 2016 Neuroscience and Behavior © Copyright by Mary Catherine Catanese 2016 All Rights Reserved ALTERATIONS TO MATERNAL BEHAVIOR AND BRAIN BY EXOGENOUS ESTROGEN EXPOSURE A Dissertation Presented by MARY CATHERINE CATANESE Approved as to style and content by ______________________________ Laura N. Vandenberg, Chair ______________________________ R. Thomas Zoeller, Chair ______________________________ Jerrold S. Meyer, Member ______________________________ Mariana Pereira, Member __________________________ Betsy Dumont, Director Interdisciplinary Graduate Programs, CNS DEDICATION To my loving Family ACKNOWLEDGEMENTS I am immensely and proFoundly grateFul to so many who have helped me on my journey through graduate school. I wish to thank my advisor and mentor Laura Vandenberg For taking me into her lab and under her wing; I am so grateFul For her wisdom, guidance and love oF science, all oF which helped to transform my experience into a joyous one. I deeply appreciate the time and work required For our studies, I have learned a great deal and Feel that we have accomplished a great deal. I wish also to thank R. Thomas Zoeller For his excellent insight, kindness, guidance, sense oF humor and encouragement. I very oFten reFlect on how Fortunate I am to have such thoughtFul, dedicated and kind-hearted mentors and advisors and Feel immensely honored to have been their student. I Feel the same way about my committee members. I thank my committee member, Jerrold Meyer For his long-term commitment to guiding and mentoring me in becoming a scientist and For his continued kindness, encouragement and support towards a career in research. I thank my committee member, Mariana Pereira, whose insight, kindness and generosity oF spirit have been greatly appreciated. To all oF you, I oFFer my deepest gratitude For your continued enthusiasm For my work and For your engagement during discussion, which oFFered many insights, improved my thinking, and my work. The many lessons oF your guidance will stay with me always. I wish to thank Gerry Downes For his kind support and Elizabeth Connor For being an excellent teaching mentor. I thank both oF them For their constant v encouragement. I wish to thank Dan Chase For taking me into his lab and giving me a project based on things other than experience and For guiding me and giving early shape to my critical thinking. I thank Zane Barlow Coleman, and Justin Fermann For their amazing mentorship and guidance while I worked on my post-baccaulareate science academic training, in order to become eligible For my graduate program. I wish to thank them For their patience and unwavering support. I wish to thank the Center For Research on Families For the Dissertation Research Award that helped me to Focus solely on my work and to accomplish so much with protected time. I wish to thank my many Friends For their unwavering support and Friendship, and my labmates and Friends From the Zoeller and Vandenberg labs, Ruby Bansal, Corinne Hill, SriDurgaDevi Kolla, Charlotte LaPlante, Sarah Sapoukey in particular For being wonderful and sharing many moments throughout this experience. I wish to thank Alexander Suvorov and Alicia Timme-Laragy For their kindness and generosity during my time here. There are so many Friends I have not named here, but I thank all oF the many Friends and acquaintances, all oF whom who have brightened my journey. I thank my Fellow NSB graduate students and Friends For many shared stories and adventures and I thank my program For making it possible For me to study neuroscience. It is an immensely proFound giFt to be able to change one’s career and to learn From so many devoted scientists. I am ever grateFul For this experience and For learning so much. vi And the last shall be First. My Family deserves and eternally possesses my love and admiration For believing in me and encouraging me throughout my graduate studies. I love you with all oF my heart and can never thank you enough. My Final thanks are For my parents. First, I wish to honor the memory oF my late Father, witnessing his illness Filled me with the need and the drive to study science, to hopeFully one day contribute to the understanding oF disease, even in some small way. I wish to thank my wonderful and loving mother, without whom none oF my accomplishments would have been possible. vii ABSTRACT ALTERATIONS TO MATERNAL BEHAVIOR AND BRAIN BY EXOGENOUS ESTROGEN EXPOSURE SEPTEMBER 2016 MARY CATHERINE CATANESE, B.A. ENGLISH, UNIVERSITY OF MASSACHUSETTS, AMHERST Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST DireCted by: Professor LAURA N. VANDENBERG Professor R. THOMAS ZOELLER Maternal care is critical For the development and long-term success oF oFFspring. Poor maternal care can have proFound eFFects on oFFspring that can last into adult liFe. Despite our understanding oF the role oF endogenous estrogen in maternal behavior, the potential eFFects oF exogenous estrogens (xenoestrogens) on maternal behavior and brain remain poorly understood. The active synthetic estrogen in contraceptive pills, 17α-ethinyl estradiol (EE2), is widely used as a positive control For estrogenicity in endocrinology and toxicology studies. Another xenoestrogen, bisphenol A (BPA) alters a broad range oF physiological processes including neural development and reproduction. Due to public health concerns with BPA, alternative compounds have been developed For use in consumer products. One replacement, bisphenol S (BPS), has not been examined extensively, but has shown estrogenic properties. Biomonitoring studies indicate that human exposures to BPS are likely to be widespread. viii Among studies that have reported eFFects oF endocrine disruptors on maternal behavior, none have concurrently examined eFFects on the regions oF the brain important to maternal behaviors. Thus, one oF the major goals oF this dissertation sought to address this gap in current knowledge. We hypothesized that low doses oF two xenoestrogens, EE2 and BPS, would disrupt maternal behavior and aFFect regions oF the brain important For maternal behavior. We Further hypothesized that neurogenesis might be one oF the critical mechanisms underlying estrogen regulated maternal behavior and that xenoestrogen exposures during pregnancy induce alterations to neurogenesis. We investigated the eFFects oF low dose exogenous estrogens on mice during pregnancy and lactation (the F0 generation), and on Females exposed during gestation and the perinatal period (the F1 generation). The work summarized in this dissertation indicates that low doses oF the synthetic estrogens EE2 and BPS alter aspects oF behavior and brain in pregnant/lactating Females, providing evidence that adults are susceptible to the disruptive eFFects oF these compounds during these vulnerable periods. Our Findings also suggest that Females are vulnerable to exposures during gestation/perinatal development, and these exposures are suFFicient to inFluence the display oF maternal behavior later in liFe. Finally, our results indicate that neurogenesis can be disrupted by xenoestrogen exposures. ix TABLE OF CONTENTS Page ACKNOWLEDGEMENTS ................................................................................... v ABSTRACT ..................................................................................................... viii LIST OF TABLES ............................................................................................. xvi LIST OF FIGURES ........................................................................................... xvii CHAPTER 1.INTRODUCTION: BEYOND A MEANS OF EXPOSURE: A NEW VIEW OF THE MOTHER IN TOXICOLOGY RESEARCH ..................................................... 1 Abstract ................................................................................................... 1 Introduction ............................................................................................... 2 IdentiFying the best methods to assess the eFFects oF EDCs .................... 4 Determining the endocrine disrupting properties oF environmental chemicals .................................. 5 Using test guidelines and non-guideline endpoints to assess endocrine disruption ............................................. 8 State-of-the-art non-guideline endpoints ..................................... 11 Maternal
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