SGI 2012: Advances in Reproductive Health Research

Abstract

The 59th Annual Meeting of the Society for Gynecologic Investigation was held in San Diego, (CA, USA) on 21–24 March 2012, with a record number of registrants (over 1300) and submitted abstracts. The main 3-day meeting was preceded by a day of satellite meetings, covering topics such as placental function, endometrial bleeding and global issues for preterm birth. The meeting was opened by the President of the Society for Gynecologic Investigation for 2011–2012, Stephen J Lye, from the University of Toronto (ON, Canada), with 13 past presidents of the society (including this writer) in attendance.

The 59th Annual Meeting of the Society for Gynecologic Investigation

San Diego, CA, USA, 21–24 March 2012

The Society for Gynecologic Investigation (SGI) promotes ‘Science in the Service of Women's Health’, and the theme of this year's meeting was personalized medicine. The President had invited Leroy Hood, President of the Institute for Systems Biology (WA, USA) to give the opening address. Hood gave his visionary perspective of future healthcare [101]: 4P medicine, that is, personalized, preventative, predictive and participatory. Hood's belief is that by taking a systems, cross disciplinary approach, linking biology and mathematics to major health challenges, we shall be able to integrate the enormous amounts of data that reflect our individual compositions and our responses to the environment around us. He views medicine as an informational science and that biological networks underpin health and disease. Perturbations of these biological networks lead to disease; therapies need to counter these perturbations. The genomic-related sciences have advanced rapidly and are continuing to develop so that each of us may soon have a personalized genome chip that will inform our individualized medical care, show which disease conditions should be of individual concern and allow the prediction of potentially successful treatment, but will place responsibility on each of us individually for elements of our good health. This SGI meeting showed further application of personalized medicine approaches to diagnosis and treatment of ovarian and breast cancers and other gynecologic cancers as well as individualized pharmacotherapy in pregnancy and across the range of women's health issues.

The developmental origins of health and disease refers to responses that the fetus makes during development, in response to adversity in the environment inside the womb, to stressors such as inappropriate nutrition, lack of oxygen or too much cortisol or other stress hormones. More recently, for some, the field has come to include responses to environmental toxins to the extent that these produce physiological change, rather than teratological insult. Recognition of the programming relationship was triggered by observations 25 years ago that birth weight is inversely related to subsequent risk of noncommunicable diseases, heart disease, osteoporosis and diabetes [1]. The developing fetus may also predict, from its intrauterine environment, what the environment will be like outside the uterus after birth. But if the fetus makes the wrong adjustment or the prediction is wrong, mismatch occurs and disease results [2]. Noncommunicable diseases such as Type 2 diabetes, metabolic syndrome and heart disease are examples of diseases that occur in later life, but which may have been ‘programmed’ in the womb. 4P personalized medicine would allow the prediction of programming, and then interventions or lifestyle adjustment. This is a fast-developing field, and there were many individual communications and a workshop session on programming at SGI, 2012. The workshop moderated by John Newnham, (University of Western Australia, WA, Australia) discussed the interactions between the environment, genetics and epigenetic change in response to altered nutrition or stress, and showed how the science of epigenetics may underpin many of these relationships, and may explain, at least in part, transmission of a condition or response from one generation to the next. Studies from the laboratory of Stephen Matthews (University of Toronto, ON, Canada) showed that exposing the fetus to exogenous glucorticoid produced permanent changes in methylation patterns of DNA in the liver, kidney and brain and these same changes persisted into the next generation's offspring [3]. Work from Mark Hanson's department (University of Southampton, UK) showed that cells in the umbilical cord had epigentically altered methylation patterns of a gene that controls blood vessel dilatation in response to hypoxemia [4]; studies from Dino Giussani's group (University of Cambridge, UK) showed that in pre-eclampsia, there is fetal brain injury due to oxidative stress and placental insufficiency, which can be treated with the antioxidant, melatonin [5]. It is becoming clear that programming will be identifiable through individual epigenetic marks on key genes, that a personalized approach may be taken early in life before manifestation of that disease and that we are on the brink of developing interventions that will counter the processes and ameliorate the disease.

A closely related and highly topical area of research relates to stem cells. Janet Rossant, a world expert on stem cells and Director of Research at the Hospital for Sick Children in Toronto (ON, Canada) gave a second Presidential lecture on this topic and discussion followed in numerous oral and poster presentations and workshop symposia. A mini symposium discussed methods involved in the isolation and characterization of stem cells and reported that genetically or epigenetically modified stem cells from the reproductive tract appear to be involved in diseases such as endometrial cancer and endometriosis. The therapeutic value of stem cells was clearly indicated by studies from Hugh Taylor's laboratory at Yale University (CT, USA), in which he had collected stem cells from bone marrow and shown that these had the potential to contribute to the endometrium after uterine injury and to improve fertility [6]. Yvonne White (Massachusetts General Hospital, Harvard Medical School, MA, USA) extended the work presented in her Presidential New Investigator lecture, in which, contrary to established textbook dogma, she showed that the human ovary contained a population of oogonial stem cells that could replenish the pool of ovarian oocytes [7,8] (see report by Harris and Polotsky [9]). She later showed that differentiation of these cells was controlled by steroid hormones, acting through a transcription factor Stra8. Estrogen-induced Stra8 expression in oogonial stem cells in vitro, suggested that this population of cells could be induced in vitro, with the clear potential for the treatment of infertility. Further studies from the same laboratory showed that this oogonial stem cell pool was important to maintain the pool of primordial ovarian follicles and that depletion of this pool contributed to ovarian aging [10]. In the same session, Wolff et al. described an induced pluripotent stem cell line from a patient with a particular precancerous endometrial polyp phenotype, which will be an important tool for studying diseases of the reproductive tract [11], and Zita et al. described reprogramming of fibroblasts into trophoblast stem cells that will facilitate studies into placental differentiation [12].

SGI has always had a strong tradition of reporting the latest work in the area of preterm labor control. At the 2012 meeting there was a special session on the microbiome and its relationship to health and disease. Organized by Roberto Romero (NIH, MD, USA; National Institute of Child Health and Human Development, MD, USA), speakers described attempts to characterize the vaginal microbiome and showed its unique and variable characteristics in comparison to the buccal and gut microbiomes. Gregor Reid (Western University, ON, Canada) gave a presentation in which he argued passionately for a role of probiotics in restoring vaginal health. He showed evidence that probiotics attenuate the proinflammatory response to the bacterial gut wall (lipopolysaccharide) and corrected a proinflammatory environment, thus demonstrating the potential to alleviate some cases of infection/inflammation-driven preterm birth. Felice Petraglia (University of Siena, Siena, Italy), in an earlier workshop dedicated to the memory of the late Wylie Vale, showed that a family of neuropeptides (the corticotrophin-releasing hormone family), present in many reproductive tissues including the uterus and placenta, produced many of the same responses. Some members of this hormone family were proinflammatory, whereas others were anti-inflammatory. Petraglia's work seemingly opened a new field of investigation into the immunomodualtory activities of these compounds in health and disease, in endometrial function and potentially in preterm labor.

A final session of special note was the mini symposium organized by Alan Bo eking (University of Toronto) which was concerned with global aspects of women's health. Highlighting that rates of maternal and neonatal mortality, and of stillbirth, are unacceptably high in many parts of the world, the symposium examined strategies that were proving effective against these events and considered how new advances in research into HIV and cervical cancer could have a global impact. Increasingly, it is being recognized that maternal malarial infection is a major factor resulting in fetal growth restriction and preterm birth; the mechanisms of this action and evolution of preventative strategies were discussed. The meeting had started with a discussion of 4P medicine and that theme was adhered throughout, from an individual to a global perspective, especially in developing countries.