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Chromosome abnormality is one of the most common causes of pregnancy loss in women. In those that survive to term, it often results in mental retardation, congenital malformation and neonatal death. The vast majority of these abnormalities are numerical and originate from maternal meiotic errors during oogenesis. The Ao lab鈥檚 main research focus is to investigate the incidence and mechanisms involved in chromosome abnormality in early human embryos and its effect in preimplantation development. The knowledge we gain by these studies not only helps our basic understanding of early human embryo development but will help us to develop new clinical approaches in assisted reproduction technology

Key words: aneuploidy, in vitro fertilization, Preimplantation genetic diagnosis, chromosome mosaicism, Infertility, Inherited genetic disease, chromosome translocation, FISH, aCGH.

The pituitary gland produces two hormones that control critical aspects of ovarian function and fertility. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) work together to promote the growth and maturation of ovarian follicles and the eggs contained within them. They also control the production of hormones like the estrogens as well as the timing of ovulation. FSH and LH are also used as drugs to treat human infertility.听 The Bernard lab investigates the processes that control the normal production and secretion of FSH and LH to better understand how these hormones may become dysregulated (uncoordinated) in different forms of female infertility, including polycystic ovary syndrome. This knowledge may lead to the development of new and more effective therapies for assisted reproduction.

The importance of the quality of sperm in the success of reproduction, whether by natural conception or with assisted reproduction, has been studied intensely in the recent years. Earlier studies on the evaluation on the quality of sperm focused mainly on motility and morphology as used in conventional semen analysis. Recently, the importance of sperm nuclear chromatin quality, sometimes referred to as sperm 鈥淒NA quality鈥�, has received attention from both researchers and clinicians. The Chan lab has focused on the evaluation, consistency and changes of sperm chromatin quality in human in various clinical scenarios. These include various pathological conditions, such as obstruction, inflammation and varicoceles, aging, exposure of various environmental toxins and chemotherapies. Knowledge generated from our lab has helped to modify the clinical practice in the management of male infertility.听

Healthy gametes are indispensable for individuals to begin families and for the human race to propagate. The female gamete 鈥� the oocyte 鈥� undergoes a prolonged period of development within the ovary, prior to ovulation, during which it undergoes a host of molecular changes that will enable it to develop as an embryo upon fertilization. Because most early pregnancy losses in humans can be traced to defects that arise in the oocyte during its development in the ovary, the Clarke lab seeks to uncover the mechanisms that regulate oocyte development and to understand how dysregulation of these mechanisms can lead to infertility. Using cell biological, molecular and genetic tools, we focus on: (i) how the oocyte establishes and maintains contact with the neighbouring support-cells of the ovarian follicle that feed it essential nutrients; (ii) how the oocyte accumulates and safely stores key molecules that the embryo will need after fertilization; (iii) recapitulating oocyte development in vitro. Our research may lead to new methods to diagnose and treat age- and disease-related infertility in women.

Dr. Culty has two main research interests: to understand what regulates the development of gonocytes, precursors of germline stem cells, and to examine the effects of environmental chemical mixtures on testis development and function. Perturbation of gonocyte development can result in infertility or testicular tumor. One of my goals is to identify factors and signaling pathways involved in gonocyte proliferation or differentiation that could help understand the mechanisms leading to testicular cancer. My other goal is to determine the impact of fetal exposure to environmental chemicals disrupting sex hormone homeostasis on spermatogenesis and steroidogenesis, using mixtures at doses relevant to human exposure. To this end, we are using a variety of molecular, cellular and biochemical approaches, on in vivo animal models, primay cells, cell lines and human tissues specimen.

The Cyr laboratory is interested in understanding the role of cell-cell interaction in the epididymis and their importance in creating a luminal environment suitable for sperm maturation. We are also interested in the effects of environmental toxicants and their effects on cell-cell interaction and in the development and function of male reproductive function.

(I) Regulation on intercellular communication: Intercellular gap junctions are essential structural components that allow direct communication between neighboring cells. Gap junctional communication is therefore critical for coordinating cellular function within complex epithelia. In the male reproductive tract, gap junctional communication is essential for the exchange of cellular messengers necessary for spermatogenesis in the testis and for the coordination of sperm maturation in the epididymis. A crucial aspect of sperm maturation is the fact that the epididymal epithelium must coordinate the different regions of epididymis in order to modify the luminal environment necessary for sperm maturation. Our objectives are to understand the role and regulation of gap junctional communication in the epididymis and their implication in sperm maturation.

(II) Epididymal tight junctions and the blood-epididymal barrier: The creation and maintenance of microenvironments within biological systems are crucial for the development and function of specialized cells within complex organisms. These microenvironments are created by tight junctions between cells which form an impenetrable seal, thereby forcing receptor mediated transport across cells and creating specific environments. These cellular barriers exist in the brain, retina, thymus, intestine, and kidney, as well as in male reproductive tissues such as the testis and epididymis. Understanding the regulation of proteins responsible for the maintenance of these barriers is necessary, as tight junctions undergo rapid alterations in diseases such as celiac disease, Crohn's disease, renal diseases, asthma, cystic fibrosis and breast cancer. In male reproductive tissues, the microenvironments formed by tight junctions are essential for spermatogenesis in the testis and for sperm maturation in the epididymis. While unexplained male infertility results from multiple causes, studies in rats have shown that infertility in ageing males is accompanied by a loss of tight junctions in the epididymis. Given the crucial nature of tight junctions in both normal physiological processes and in widespread pathologies, including male infertility, our objective is to understand the factors regulating the formation of the tight junctions responsible for the formation of the blood-epididymal barrier, a key determinant of male fertility.

Ovary is the female reproductive organ that contains a finite number of meiotically arrested oocytes that need to be released into uterus during each reproductive cycle throughout a females (reproductive) life. Ovulation is a result of tightly regulated development and maturation of oocytes within the structures called ovarian follicles. In the Duggavathi lab, our research focuses on mechanisms of regulation of female fertility with emphasis on ovarian follicular granulosa cells. Our current research involves two modules. In module 1, we use genetically and pharmacologically manipulated mouse models to investigate signaling pathways governing granulosa cells functions. In module 2, we use bovine model to investigate metabolic regulation of ovarian function in dairy cows. We use cutting-edge molecular biology techniques such as laser micro dissection, chromatin immunoprecipitation, immunobloting, quantitative-PCR among others for our research.

Key Words: Ovulation, fertility, granulosa cells, signaling pathways, conditional knockouts, dairy cows, dominant follicle.

A leading cause of infertility is a defect in the woman鈥檚 egg (oocyte) that causes it to have the wrong number of chromosomes. These so-called 鈥榓neuploid鈥� oocytes cause developmental conditions such as Down鈥檚, and can lead to pregnancy loss. These errors become increasingly common with advancing maternal age, and are therefore a major reason why older women experience difficulties establishing a healthy pregnancy.听

The part of the cell responsible for maintaining the correct chromosome number is the spindle - a complex biological machine that gathers and sorts chromosomes at the time of cell division, and dispatches them to the two daughter cells in a process termed chromosome segregation. Why chromosome segregation often goes wrong in oocytes is poorly understood. Once the oocyte is fertilised the first several cell divisions in the newly forming embryo are also highly prone to chromosome miss-segregation. These embryonic errors are also associated with decreased fertility, but their causes and consequences remain obscure.

Research in our laboratory is aimed at understanding how healthy eggs and embryos are made, and we are particularly focussing on how and why defects in chromosome segregation can cause infertility. We specialise in the use of cutting edge microscopy techniques to analyse egg and embryo function ex-vivo. We have important collaborators in Montreal and elsewhere, including close collaborations with Hugh Clarke of the CRRD, and the MUHC assisted reproduction facility.

Ongoing projects in the lab include:

• Analysis of spindle microtubule dynamics in oocytes.
• Evaluation of the changes in spindle function that occur with maternal age, and how this causes chromosome segregation error.
• Analysis of the mechanism of chromosome segregation in embryos, and the causes of segregation errors.
• Analysis of apoptotic pathways in oocytes and embryos.
• Analysis of spindle pole focussing and centriole development in mammalian embryos

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The lab is currently financed by funding from CIHR, NSERC, and Fondation Jean-Louis L茅vesque.

In the Goodyer lab, we are studying the role of the growth hormone (GH)-insulin-like growth factor (IGF-I) axis during human fetal and postnatal growth (idiopathic short stature) as well as obesity and cancer.听 Our major focus is characterizing what regulates expression of the GH receptor (GHR) in GH target tissues as GHR levels have a major influence on responsiveness of these tissues to GH. We are also interested in the effects of certain chemical contaminants found in our everyday environment (flame retardants) on development and functioning of the human male and female reproductive systems.听 Our clinical/epidemiological studies suggest that these chemicals have potential endocrine disruptor effects on both the testes and the ovary.

Key Words: developmental endocrinology, Growth Hormone (GH), GH receptor, fetal and childhood growth, obesity, cancer, environmental contaminants, flame retardants, endocrine disruptors

The Gupta laboratory is interested in understanding the molecular and cellular basis of congenital kidney and urinary tract disorders in children.听 There are three projects that all focus on this theme. In one project, we are understanding the biology and genetics of a common urinary tract disorder known as vesico-ureteric reflux that causes recurrent urinary tract infections in children.听 In a second project with the Ryan laboratory, we are exploring the roles of the claudin tight junction proteins during kidney development and in children with congenital renal malformations.听 In the third project with the Takano laboratory, we are understanding the basis of a specific kidney disease that affects the podocytes known as nephrotic syndrome.

Key Words: congenital kidney and urinary tract disorders, vesico-ureteric reflux, nephrotic syndrome

The goal of the HALES lab is to determine the underlying mechanisms by which a teratogenic insult dysregulates embryo development.听 Topics of research in our lab today include: teratogen-induced signaling pathways during embryo development; the effects of flame retardants in house dust on progeny outcome; the impact of exposure to phthalates, their metabolites and "green" plasticizers on reproductive health; and consequences of treatment with venlafaxine, an antidepressant commonly prescribed during pregnancy, on fetal development. Using in vivo and ex vivo animal models we have contributed to our understanding of the effects of developmental toxicants on development. We have shown that the oxidative stress and DNA damage response pathways play a critical role in mediating developmental toxicity. We have demonstrated that teratogen exposures activate hypoxia and p53 signaling in the limb. Recent studies have focused on the action of developmental toxicants on epigenetic marks, such as target acetylation, in regulating the expression of transcription factors such as Sox9 and Runx2 that are critical during development. In addition, we collaborate with the Robaire lab to determine the consequences of preconception paternal exposure to anticancer drugs on germ cell quality and progeny outcome.

Research in the Head lab is focussed on the effects of environmental chemicals on the health of birds. 听Our research is multidisciplinary, integrating aspects of molecular toxicology听and avian ecology. 听In the laboratory we use molecular听techniques to describe mechanisms of action of toxic substances. 听A current focus is on genetic and epigenetic factors that modulate avian responses to polycyclic aromatic hydrocarbons (PAHs)听through the aryl hydrocarbon receptor (AHR) pathway. 听In the field, we apply what we have learned to assess the health of wild birds. 听We measure biomarkers of chemical听exposure, hazard, or susceptibility, and make predictions about health at the level the level of the individual, population, or species. 听A current interest is in how the early environment of a developing avian embryo prepares that individual for a lifetime of exposure to environmental contaminants.听

Key Words:听听ecotoxicology, toxicants, avian, PAH, AHR, epigenetics, DNA methylation, species sensitivity, biomarkers, development

The focus of the Jerome-Majewska lab is the identification and characterization of genes responsible for congenital syndromes that disrupts formation of the face and placenta. We use next-generation sequencing to identify genes and genome editing to generate appropriate mouse models. Identifying and understanding the genetic and molecular basis of abnormal development is an essential first step for genetic counselling of families affected and the eventual identification of targetable pathways for drug discovery.

The Kimmins research program focusses on the epigenome, a heritable layer of biochemical information that takes the form of methylation of DNA and the post-translational modification of chromatin associated proteins, the histones. The epigenome has been implicated in complex diseases such as cancer, diabetes, schizophrenia and autism.听 There is enormous potential in disease treatment and prevention via increased understanding of the establishment of the epigenome in development. Unlike the genome, the epigenome is dynamic and responds to environmental influences. We are interested in how environmental exposures to the father such as poor diet and toxicants can interact with the developing sperm, and how this is transmitted to the embryo. We explore these research questions using transgenic mouse models to establish critical molecular underpinnings, which are then translated and studied in humans.听 Long-term goals are to develop pre-conception advice for men and intervention strategies to improve child and adult health.

Key Words: epigenetics/epigenome, transcriptomics, epigenetic-inheritance, nutrients, toxicants, pharmacology, physiology, infertility, parental disease transmission, development, transgenics, epigenetic-environment interactions听

The Monnier research program focuses on the impact of the environment (including assisted reproductive technologies) on reproductive health. Several American and European studies have reported an impairment of spermiologic parameters for about forty years. Among hypothetic causes they point at environmental factors as several environmental chemical contaminants have been identified as endocrine disrupters. Exposure to one or more of these factors right from peri-conceptional period may have an impact on adult reproductive health. Among endocrine disrupters, a group of man-made chemicals used as plasticizers (including phthalates and bisphenol A), have recently received special attention because of their high-volume production, ubiquitous environmental presence, and possible association with adverse reproductive health outcomes. We are participating in two cohort studies to analyze the impact of plasticizers on pregnancy outcome, fetus and infant sexual development. We are also contributing to a team grant about the potential impact of brominated flame retardants on reproductive health. Long-term goals are to develop pre-conception advice for couples to improve pregnancy outcomes, child and adult health.

Key Words: endocrine disruptors 鈥� reproductive health 鈥� phthalates 鈥� brominated flame retardants

Spermatozoa form in the testis during spermatogenesis. However, the resulting sperm are immature and incapable of fertilization. As the spermatozoa migrate through the epididymis they encounter a host of luminal proteins, some of which mediate biochemical modifications that transform sperm into a fertile state, a process termed 鈥渕aturation鈥�. A selective uptake and loss of epididymal glycoproteins along with modifications of the lipid composition (reduction of cholesterol/phospholipid content and desulfation of glycolipids) of the sperm plasma membrane has been observed to occur during epididymal transit. This appears to be essential in establishing the fertilizing ability of spermatozoa.听 The Morales lab investigates the effect of several sphingolipidoses and their negative consequences in fertility.

Dr. Makoto Nagano initiated the research of male germ line stem cells with Dr. Ralph L. Brinster immediately after he invented spermatogonial transplantation, the innovative assay system that functionally and unequivocally detects spermatogonial stem cells (SSCs). Since then, he has contributed significantly to the development of the research field. His ongoing research focuses on two critical issues in SSC research. One is to generate a fate map of SSCs in mice and humans (how SSCs commit to differentiation and what occurs during the process at the molecular, epigenetic, and protein levels). The other is to apply human SSCs to clinical settings, including developing a reliable and reproducible human SSC culture to expand them and assess their integrity during the culture period.听

O鈥橣laherty Lab research interest focuses on the molecular mechanisms that drive the production of mature spermatozoa and their modulation by reactive oxygen species (ROS). The oxidative stress, a condition characterized by high levels of ROS and/or low levels of antioxidant systems, can induce damage on spermatogenesis and sperm maturation, leading to an increase of defects in the paternal genome and impairment of motility and the acquisition of fertilizing ability by the spermatozoon. High levels or ROS haven associated with specific reproductive conditions, lifestyles, exposure to environmental toxicants and drugs, affecting the quality of spermatozoa. On the other hand, low ROS levels trigger and modulate signaling pathway necessary for the spermatozoon to achieve fertilizing competence. We aim to identify molecular mechanisms modulated by ROS during spermatogenesis, epididymal sperm maturation and capacitation. We recently characterized a newly discovered family of antioxidant enzymes called Peroxiredoxins (PRDXs) that play a major role in the protection of human spermatozoa against oxidative stress. Reduced activity or absence of PRDXs are associated with male infertility (humans and animal models). Our ultimate goal is to develop novel diagnostic and therapeutic approaches to help infertile men.

Key words:听Male reproduction, reactive oxygen species, oxidative stress, sperm capacitation, male infertility, antioxidants, fertilization, embryo development

Research in the Papadopoulos lab focuses on understanding the cellular and molecular mechanisms responsible for the initiation and maintenance of steroid biosynthesis in the gonads, adrenal, and brain, in health and disease. The lab also studies the regulation of steroid biosynthesis, intracellular compartmentalization of cholesterol by hormones, chemicals, drugs and environmental factors. Our goals are to understand the pathophysiology of steroidogenesis, develop new tools for the treatment of diseases related to elevated or low steroid levels, and alter subcellular steroid compartmentalization as a means to block disease acquisition and/or its progression. In these studies, we use biochemical, pharmacological, and molecular methods, as well animal models of disease and human specimens, to identify the pathophysiological role of critical components of the steroidogenic pathway. Drug design methods and molecular modeling help us modify existing chemical entities and generate novel ones targeted at key elements of the steroidogenic machinery.

Key words: steroids, neurosteroids, pharmacology, drug discovery, endocrinology

Over the past 20 years, there has been s a clear trend for men to start having children at an increasingly older age. While it is well recognized that there is an association between maternal age and decreased fertility, higher incidence of abnormalities and diseases in their children; we are only beginning to grasp the impact of paternal age on fertility and progeny outcome. This is where the Robaire lab鈥檚 research interests lie, focusing on male-mediated reproductive toxicology, aging of the male reproductive system, mechanisms of androgen actions, and the structure, function, and regulation of the epididymis.听

Epithelial cell layers often act as structural barriers that either protect against pathogens or separate tissues into physiologically distinct compartments.听 However, during embryonic development they are extremely fluid and undergo dynamic remodelling.听 During all of these behaviours, the integrity of the epithelium is maintained through intercellular junctions.听 The Ryan lab explores the function of the claudin family of tight junction proteins, whose members regulate paracellular permeability, apical-basal cell polarity and cell adhesion, and link the tight junction to the actin cytoskeleton. Through these activities, claudins have the potential to coordinate cell and tissue behaviours.听 However, the cellular mechanisms underlying their actions remain undefined.听 We are investigating the unique functions of individual claudins during neural tube closure, heart development, branching morphogenesis in the kidney and migration of germ cells to the stem cell niche.

Key words: embryonic development, neural tube closure, epithelial polarity

A hydatidiform mole is an aberrant human pregnancy with no embryo that has fascinated and puzzled scientists in all civilizations. This condition is of ancient recognition and its description figures in Hippocrates鈥� manuals under the name of "dropsy of the uterus." The sporadic form of hydatidiform moles is common and occurs in 1 in every 600 pregnancies in western countries, but at higher frequencies in other parts of the world. By analyzing rare familial cases of hydatidiform moles, Dr. Slim鈥檚 group identified the first defective maternal gene, NLRP7, responsible for this condition. NLRP7 is a member of a family of proteins with roles in inflammation and apoptosis. The current research activities of her group are focused on (i) elucidating the exact role of NLRP7 in the pathophysiology of moles and (ii) identifying new genes for this condition. Their goals are to better understand this condition and be able to help more patients by providing appropriate DNA testing and genetic counseling.

Women鈥檚 fertility depends on the number and quality of oocytes in reserve, both of which are established by birth and decline with age. The oocyte reserve is limited because all oogonia stop proliferation and enter meiosis in fetal life, and, in addition, more than half of the initial oocyte population is eliminated before birth. During this period, homologous chromosomes pair, synapse and recombine; these events are essential for securing proper chromosome segregation in oocytes and generating genetic diversity in the offspring. The main hypothesis in the Taketo lab is that a failure in meiotic synapsis leads to apoptotic elimination of oocytes carrying asynapsis, thus minimizing the risk of aneuploidy in embryos. Specifically, we will (1) clarify the regulatory mechanism of the caspase 9-mediated apoptotic pathway responsible for oocyte elimination, (2) determine the mechanism by which persistent chromosome asynapsis leads to oocyte demise, and (3) assess the integrity of oocytes which have survived when apoptotic elimination is circumvented. We are also interested in the regulation of spindle assembly and chromosome segregation during the second meiotic division in mature oocytes.

Research in the Trasler lab focuses on epigenetics as it pertains to normal development in children and the prevention of birth defects.听 The epigenome provides a way for the environment to interact with our genomes to modify gene expression in ways both adaptive and maladaptive and undergoes its most dramatic remodeling in germ cells and early embryos. Ongoing projects include studies of normal and abnormal DNA methylation programming, genomic imprinting and the molecular and cellular targets for drug effects on germ cells and embryos. We are examining effects of drugs, diet (folate) and assisted reproductive technologies on the epigenome of germ cells and embryos and the implications for intergenerational passage of epigenetic defects.听 Our clinical focus is the 10-20% of couples who suffer from infertility or delay child-bearing and increasingly (1-6% of pregnancies) resort to the use of assisted reproductive technology. Both infertility and the use of assisted reproductive technology are associated with epigenetic (DNA methylation) defects and adverse outcomes in children. Our long term goal is to better understand how the environment interacts with our genes through the epigenome during development to find new approaches to the prevention of birth defects in children.

Key words: epigenetics, birth defects, DNA methylation, genomic imprinting, assisted reproductive technology, folate, germ cells, infertility, embryogenesis

Dr. Hope Weiler 's research focus is on mineral and lipid nutrients, including vitamin D, and the role in bone mineral acquisition in children and maintenance in adulthood in urban and Indigenous populations in Canada. She is the co-chair for the National Inuit Health Surveys Working Group and administrative principal investigator managing the International Polar Year Inuit Health Survey of 2007-2008.听

Producing normal sperm is critically important for the transmission of the hereditary information encoded in our DNA from one generation to another.听 In order to produce these highly specialized germ cells that are capable of swimming to the egg and fertilizing it, a number of changes in cellular structure and function must be made.听 These changes are mediated in part by degrading proteins that are no longer needed in the mature sperm.听 The Wing laboratory studies the role of a protein degradation system called the ubiquitin proteasome system.听 Recent results have demonstrated that dysfunction in an enzyme in this system leads to defects in both the formation and maintenance of the stem cells in the testis that generate the sperm.听 Understanding the fundamental mechanisms underlying the generation of sperm will help us diagnose male infertility more precisely and may lead to novel approaches to treatment of infertility.

Dr. Yojiro Yamanaka is a developmental and stem cell biologist. Since he started his own laboratory in 2009 at 捆绑SM社区, his lab is interested in molecular and cellular mechanisms of epithelial morphogenesis and cell plasticity in early mammalian embryos and in embryonic stem cells. The lab has developed various unique techniques, such as a method to microinject small molecules (mRNAs, cDNAs etc) into early mouse blastomeres and a live imaging system to observe developing pre- and post- implantation embryos.. Currently, he is the director of the transgenic facility at the Goodman Cancer Research Centre.听 His lab is very familiar to use novel engineer endonucleases, ZFNs/TALENs/CRISPR-Cas9. A part of his lab and the transgenic facility are working closely to develop new genome modification strategies using CRISPR/Cas9 technology.听听

Male infertility is associated with poor sperm DNA quality and several studies have reported that tests of sperm DNA and chromatin integrity may be better markers of male fertility potential than conventional sperm parameters. The Zini lab is interested in the evaluation of markers of sperm DNA and chromatin integrity. The Zini lab examines the effects of male-specific therapy (e.g. varicocelectomy, antioxidant therapy) on sperm chromatin integrity. The lab is also involved in developing sperm separation techniques that allow for recovery of sperm with high DNA integrity.