Lecture Abstract

Division of Fertility Preservation

Lecture Abstract

Teresa K. Woodruff, Ph.D. The Thomas J. Watkins Professor of Obstetrics and Gynecology, The Feinberg School of Medicine, Northwestern University, Chicago, IL

Recognizing the unmet fertility management needs of women facing fertility threats, the Department of Obstetrics and Gynecology took an unprecedented step and created a new clinical division, the Division of Fertility Preservation in the fall of 2006. The mission of the division is to increase the pace and quality of basic ovarian research and to provide fertility sparing options to young adults with a cancer diagnosis as well as other fertility threatening diseases or disease treatments. Members of the division explore the molecular mechanisms that underlie normal follicle development, develop methods that support human follicle development and provide information, support and guidance to reproductive-age cancer survivors and other young adults to accelerate research in fertility preservation. In achieving our mission, the Division of Fertility Preservation is meeting the needs of women within our local community and providing a template for work around the nation.

Dr. Teresa K. Woodruff, a leader in the field of reproductive research, heads the division. Dr. Woodruff is a professor of obstetrics and gynecology and of endocrinology at the Feinberg School of Medicine and professor of biochemistry, molecular biology and cell biology in the Weinberg College of Arts and Sciences, She was appointed the Thomas J. Watkins Memorial Professor in Obstetrics and Gynecology in 2006 and is the immediate past director for the basic science programs of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Woodruff’s career focuses on ovarian biology and interdisciplinary approaches to solving problems in reproductive sciences. Her team has led the way in the new discipline of oncofertility, encountering patients at the time of a cancer diagnosis, and navigating the patient through the decision making process about fertility and, in some specialized cases, providing the fertility preservation interventions.

The programs within the Division of Fertility Preservation encompass cutting edge research and advanced clinical care. The Division serves as the coordinating unit between the specialties that comprise the new discipline, created by Dr. Woodruff and coined “oncofertility”. The participating disciplines include oncology, gynecological oncology, urology, reproductive endocrinology, pathology, biomedical engineering, molecular biology and the behavioral and social sciences including bioethics, health law, policy studies, economics and communication science. The Division also serves as a centralized resource for information about fertility management for clinicians and cancer survivors while working closely with the Robert H. Lurie Comprehensive Cancer Center (recently designated a Center of Excellence by Fertile Hope, the nation’s leading advocacy organization dedicated to fertility preservation for cancer survivors).

The Division’s goals include:

Encouraging research that can protect or preserve fertility for reproductive-aged cancer survivors
Expediting the transition from research findings to clinical practice
Understanding the decision-making process that cancer patient face when dealing with the potential loss of fertility
Serving both the professional and general communities as a resource for fertility preservation
Navigating reproductive age cancer survivors through the clinical options for fertility preservation

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The Division of Fertility Preservation Abstract

Lecture Abstract

The Division of Fertility Preservation abstract

Institute for Women’s Health Research

Lecture Abstract

Teresa K. Woodruff, Ph.D. The Thomas J. Watkins Professor of Obstetrics and Gynecology, The Feinberg School of Medicine, Northwestern University, Chicago, IL

Northwestern University’s Institute for Women’s Health Research is helping to accelerate the rate of discovery in the sciences that impact women’s health and well-being. Led by internationally renowned researcher Teresa K. Woodruff, PhD, the Institute delivers on Northwestern’s vision for collaboration by creating uncommon teams of researchers and applying innovative problem solving. The Institute and its team are also leveraging Northwestern’s growing reputation for excellence in women’s clinical care by catalyzing the strengths and resource of the Feinberg School of Medicine, the University and Northwestern Memorial’s new state-of-the art Prentice Women’s Hospital. Together, we will make Chicago an epicenter of women’s health research and care.

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Pushing the boundaries of women’s health research.

http://www.womenshealth.northwestern.edu/

The Institute for Women's Health Research Abstract

Lecture Abstract

The Institute for Women's Health Research abstract

Inorganic Signatures of Life

Lecture Abstract

Teresa K. Woodruff, Ph.D. The Thomas J. Watkins Professor of Obstetrics and Gynecology, The Feinberg School of Medicine, Northwestern University, Chicago, IL and Thomas V. O’Halloran, Ph.D. The Morrison Professor of Chemistry, The Weinberg College of Arts and Sciences, Evanston, IL.

Little is known about the signaling networks that support the integration of the male and female germ cells into a new totipotent cell, the one-cell embryo. We propose that heretofore poorly understood inorganic signaling molecules initiate the massive changes in the physiology of a fertilized egg. Based on preliminary studies, the team hypothesizes that fluxes in zinc ions mediate the first definitive signal in embryonic development. This hypothesis will be tested by two approaches: one targets real time changes in the subcellular concentrations of free zinc and calcium in live cells and the other rigorously maps specific changes in the total zinc pools at the nanometer level. The mouse oocyte is an ideal model system to study this novel inorganic signaling pathway. It undergoes a clear developmental pattern of receptor-mediated events as it transitions from a dormant stage to a fully active state upon fertilization. Also, its large size facilitates spatial localization of key molecular players. New analytical tools will be developed to map the abundance of specific inorganic molecules and biological receptors.

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This work is supported by A Keck Foundation Grant, The Vice President for Research, Northwestern University, The Chemistry of Life Processes Institute, the Institute for Women’s Health Research,
and the Chicago Biomedical Consortium.

New Insights into Inhibins and Activins

Lecture Abstract

Teresa K. Woodruff, Ph.D. The Thomas J. Watkins Professor of Obstetrics and Gynecology, The Feinberg School of Medicine, Northwestern University, Chicago, IL

The TGFβsuperfamily arose millions of years ago and co-opted a transmembrane receptor with serine-threonine kinase properties. The modern family consists of forty-two encoded subunits, five binding receptors (RII) that are constitutively active serine-threonine kinases, and seven signaling receptors (RI) that are RII substrates. The ligands in this family are dimers that are disulfide linked in most, but not all cases. A large number of ligands can be produced from the subunit family and interact with a limited array of receptor partners. Therefore, the evolutionary pressure for the TGFβ superfamily was to build regulatable ligands rather than to expend energy on a larger set of receptors. The three activin isoforms [activin A (βA-βA), activin B (βB-βB) and activin AB (βA-βB)] are regulated independently and have distinct biological functions. Activin is a unique ligand within the TGFβ superfamily because it has a naturally occurring antagonist call inhibin. Inhibin is the only endocrine hormone in the TGFβsuperfamily and blocks the paracrine acting activin in a classically defined negative feedback loop. One of the reasons that the ligands act as functional antagonists is their structural similarity. Activin is a dimer of two TGF-like βsubunits, while inhibin is assembled from a βA- or βB-subunit and a dissimilar αsubunit. Inhibin is known to bind the activin receptor ActRIIB, with the aid of an accessory protein known as betaglycan. Mammalian α-subunits are not able to homo-dimerize and regulation of α-β heterodimers vs. β-β homodimers is just one of the major cellular problems that had to be solved. The ovarian granulosa cell produces both ligands, whereas inhibin B is the dominant form produced by Sertoli cells. Loss of inhibins at the time of menopause in women, following Sertoli damaging chemotherapy in men, or by experimental interventions leads to a prodigious increase in FSH production, indicating that these ligands are central to FSH restraint in an endocrine manner. Our studies have provided insights into the control of inhibin and activin action and to a more complete understanding of normal fertility and the mechanisms that underlie reproductive diseases in women resulting from inappropriate hormone action.

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Ensuring a healthy life and prevention of disease in women through research partnerships.

This work is supported by NIH/NICHD Hormone Signals that Regulate Ovarian Differentiation, P01 HD021921; NIH/NICHD, Inhibin Actions on Reproductive Target Tissues, R01 HD37096; and, NIH/NICHD, Regulation of Reproductive Function by Activin.

Oncofertility: The Preservation of Fertility Options for Young People with Cancer

Lecture Abstract

Teresa K. Woodruff, Ph.D. The Thomas J. Watkins Professor of Obstetrics and Gynecology, The Feinberg School of Medicine, Northwestern University, Chicago, IL

Cancer is now a disease with a variety of treatment options, which are leading to longer and more productive lives by survivors. Globally, there are 10 million people diagnosed with cancer. 10% of these newly diagnosed men and women are under the age of 45 years old. Infertility can be a consequence of many of the more aggressive chemo- and radiation therapies that prolong and save lives. The ability to easily preserve sperm prior to cancer treatment provides hope at the time of diagnosis and families later in life for male survivors. A notable example is Tour de France winner Lance Armstrong who has three children conceived using sperm frozen days before he underwent the massive chemo- and radiation therapy that saved his life. Unlike sperm, the female germ cell, the oocyte or egg must be retrieved surgically. Moreover, the vast majority of collected oocytes will be immature and cannot be used immediately by a woman who is ready to start a family. The overall hypothesis of the program is that effective fertility-extending options can be provided to young women undergoing life-preserving cancer treatment. The purpose of our work is to bring physicians, medical ethicists, social scientists and basic scientists together to develop new strategies for fertility preservation for female cancer survivors under the new discipline of oncofertility. And even as the lexicon is being established, complex bioethical issues face both providers and parents. At the basic science level, complex issues of ovarian function and preservation must be addressed including the problem of follicle growth and development in vitro. Our investigative group has pioneered the development of a 3-dimensional system that supports follicle development, largely, we believe, because the links between the egg and its surrounding cells are maintained. Using a tissue-engineered approach, we have developed an in vitro follicle growth system that supports the maturation of the enclosed oocyte, which can be fertilized and results in live, healthy and reproductively competent mice. The goal of our program and the broader Oncofertility Consortium is to explore and expand the reproductive options available to young people facing a fertility-threatening but life-preserving cancer treatment.

The Oncofertility Consortium logo is a trademarked advocacy ribbon that reflects the growing concern for the reproductive future of cancer patients. The intertwining spring green and hearty purple represents blossoming hope and uncompromised dedication to improving fertility preservation options for cancer patients. The lower tip of the ribbon emerges shows an emergence of eggs or embryos, as well as sperm, welcoming the translation of current research to the improvement of fertility options for all cancer patients. The ribbon has a slightly ‘bowed’ shape, providing a subliminal imagery of a fertile state.

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Exploring and expanding options for the reproductive future of cancer survivors.

This work is supported by NIH/NICHD Structure-Function Relationships in Reproductive Science, U54 HD041857; and, the Oncofertility Consortium, UL1DE019587 and RL1HD058295
http://oncofertility.northwestern.edu/

Center for Reproductive Research

Lecture Abstract

Structure-Function Relationships in Reproductive Biology

Teresa K. Woodruff, Ph.D. The Thomas J. Watkins Professor of Obstetrics and Gynecology, The Feinberg School of Medicine, Northwestern University, Chicago, IL

The Center for Reproductive Research (CRR) at Northwestern University has as its goal to contribute to a more comprehensive understanding of female fertility and infertility. The purpose of our center is to explore ovarian follicle dynamics from the perspective of structure-function relationships of the follicle unit and the hormones that regulate it. Our intent is to facilitate the transfer of basic biological, biochemical and biophysical findings to clinical care by bringing experts in engineering, biophysics and structural biology together with reproductive endocrinologists and clinical investigators. In the first five years of the center, we explored the relationship between the holo-follicular structure and its ability to sense and respond appropriately to endocrine hormones and paracrine acting factors (inhibin and activin) and made significant new observations about how these mechanisms are regulated biophysically. We solved four major hormone structures at the atomic level and the structure of a transcription factor bound to DNA. We also developed an in vitro follicle maturation system that supports immature follicle growth, oocyte maturation and the birth of live, healthy offspring. By all measures, the center has been productive and effective in translating the work from basic reproductive biology to biophysics and biomaterials to the bedside. The next five years of work are innovative and again focus on major questions in reproductive science using a structure-function approach. Our scientists and clinical investigators work as a highly effective team to ensure the timely, bidirectional transfer of information from clinical problem to the bench and back. To accomplish our goals, four projects are proposed. It is known that fertility and oocyte quality diminish with age and oocytes from older women frequently have abnormal meiotic spindles, including abnormal chromosome alignment and microtubular matrix composition and aneuploidy. Lonnie Shea and team (Project I) developed an in vitro follicle maturation system, an attractive model for exploring age-related oocyte health. They will test the hypothesis that oocyte abnormalities arise from lack of coordinated growth of the holo-follicular complex. Kelly Mayo and Ishwar Radhakrishnan (Project II) will continue their exploration of transcription factor interactions that direct hormone-dependent gene expression in the granulosa cell. Specifically, they will ask how SF-1 and LRH-1 nuclear receptors regulate inhibin α-subunit gene expression at the molecular level in conjunction with the cAMP-dependent factor CREB and the ovarian factors GATA-4 and GATA-6. Project III is led by Ted Jardetzky, who is studying the atomic structure of TGF-β superfamily ligands in complex with regulating binding proteins. He is specifically interested in oocyte-derived GDF-9 and BMP-15, which control follicle development. Finally, Project IV will examine the relationship of structural rigidity to follicular function and is collaboration between Teresa Woodruff and Andrea Dunaif. By combining basic biochemical, biomaterial and biophysical approaches with medicine, we will remain at the forefront of new discoveries in the structure-function relationships of reproductive biology. Moreover, each of our continuing projects reaffirms our commitment to translate our findings to the bedside, and thereby contribute to the overall health of women.

Center for Reproductive Research web site

Center for Reproductive Science web site

This work is supported by NIH/NICHD Structure-Function Relationships in Reproductive Science, U54 HD041857.