J. R. G. Challis

Simon Fraser University, Burnaby, British Columbia, Canada

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Publications (482)1741.33 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the effects of betamethasone on fetal growth and neonatal outcomes. A retrospective cohort study was performed of deliveries that occurred at Charité University Hospital Berlin, Germany, between January 1996 and December 2008. The betamethasone group included women with preterm labor and symptomatic contractions, cervical insufficiency, preterm premature rupture of membranes, or vaginal bleeding. Women in the control group were matched for gestational age at time of delivery and had not received betamethasone. Fetal growth changes and neonatal anthropometry were compared. Among 1799 newborns in the betamethasone group and 42 240 in the control group, betamethasone was associated with significantly lower birth weight (154g lower on average) after adjusting for confounders (e.g. hypertension, smoking, and maternal weight), sex, and gestational age at delivery (P<0.05). The higher the dose, the greater the difference in mean birth weight versus controls in births before 34(+0)weeks (≤16mg -444g; 24mg -523g; >24mg -811g), without a detectable improvement in neonatal morbidity or mortality. There was a dose-dependent decline in expected fetal weight gain as estimated by serial ultrasonography examinations 6-8 weeks after betamethasone administration (P<0.05). Betamethasone exposure reduces fetal weight gain in a dose-dependent manner without improving neonatal morbidity or mortality. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
    International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 03/2015; 130(1). DOI:10.1016/j.ijgo.2015.01.013 · 1.54 Impact Factor
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    Siwen Yang · Gregor Reid · John R G Challis · Sung O Kim · Gregory B Gloor · Alan D Bocking ·
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    ABSTRACT: Preterm birth (PTB) continues to be a global health challenge. An over-production of inflammatory cytokines and chemokines, as well as an altered maternal vaginal microbiome has been implicated in the pathogenesis of inflammation/infection-associated PTB. Lactobacillus represents the dominant species in the vagina of most healthy pregnant women. The depletion of Lactobacillus in women with bacterial vaginosis (BV) has been associated with an increased risk of PTB. It remains unknown at what point an aberrant vaginal microbiome composition specifically induces the cascade leading to PTB. The ability of oral or vaginal lactobacilli probiotics to reduce BV occurrence and/or dampen inflammation is being considered as a means to prevent PTB. Certain anti-inflammatory properties of lactobacilli suggest potential mechanisms. To date, clinical studies have not been powered with sufficiently high rates of PTB, but overall, there is merit in examining this promising area of clinical science.
    Frontiers in Immunology 02/2015; 6:62. DOI:10.3389/fimmu.2015.00062
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    ABSTRACT: The effects of endogenous cortisol on binucleate cells (BNCs), which promote fetal growth, may be mediated by glucocorticoid receptors (GRs), and exposure to dexamethasone (DEX) in early pregnancy stages of placental development might modify this response. In this article, we have investigated the expression of GR as a determinant of these responses. Pregnant ewes carrying singleton fetuses (n = 119) were randomized to control (2 mL saline/ewe) or DEX-treated groups (intramuscular injections of 0.14 mg/kg ewe weight per 12 hours) at 40 to 41 days of gestation (dG). Placental tissue was collected at 50, 100, 125, and 140 dG. Total glucocorticoid receptor protein (GRt) was increased significantly by DEX at 50 and 125 dG in females only, but decreased in males at 125 dG as compared to controls. Glucocorticoid receptor α (GRα) protein was not changed after DEX treatment. Three BNC phenotypes were detected regarding GRα expression (++, +-, --), DEX increased the proportion of (++) and decreased (--) BNC at 140 dG. Effects were sex- and cell type dependent, modifying the responsiveness of the placenta to endogenous cortisol. We speculate that 3 maturational stages of BNCs exist and that the overall activity of BNCs is determined by the distribution of these 3 cell types, which may become altered through early pregnancy exposure to elevated glucocorticoids.
    Reproductive sciences (Thousand Oaks, Calif.) 10/2014; 22(5). DOI:10.1177/1933719114553452 · 2.23 Impact Factor
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    ABSTRACT: Glucocorticoid treatment given in late pregnancy in sheep resulted in altered placental development and function. An imbalance of placental survival and apoptotic factors resulting in an increased rate of apoptosis may be involved. We have now investigated the effects of dexamethasone (DEX) in early pregnancy on binucleate cells (BNCs), placental apoptosis, and fetal sex as a determinant of these responses. Pregnant ewes carrying singleton fetuses (n = 105) were randomized to control (n = 56, 2 mL saline/ewe) or DEX treatment (n = 49, intramuscular injections of 0.14 mg/kg ewe weight per 12 hours over 48 hours) at 40 to 41 days of gestation (dG). Placentomes were collected at 50, 100, 125, and 140 dG. At 100 dG, DEX in females reduced BNC numbers, placental antiapoptotic (proliferating cell nuclear antigen), and increased proapoptotic factors (Bax, p53), associated with a temporarily decrease in fetal growth. At 125 dG, BNC numbers and apoptotic markers were restored to normal. In males, ovine placental lactogen-protein levels after DEX were increased at 50 dG, but at 100 and 140 dG significantly decreased compared to controls. In contrast to females, these changes were independent of altered BNC numbers or apoptotic markers. Early DEX was associated with sex-specific, transient alterations in BNC numbers, which may contribute to changes in placental and fetal development. Furthermore, in females, altered placental apoptosis markers may be involved.
    Reproductive sciences (Thousand Oaks, Calif.) 07/2014; 22(1). DOI:10.1177/1933719114542028 · 2.23 Impact Factor
  • Kent L R Thornburg · John R G Challis ·
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    ABSTRACT: By any of several measures, the health of the American population has been worsening over the last two decades. Obesity, type 2 diabetes and heart failure have risen dramatically. All the while, the average birthweight at all gestational ages has declined. The relationship between robust growth in the womb and lifelong health is now well established. Likewise, babies born at the low end of the birthweight scale are known to have highly elevated risks for ischemic heart disease, hypertension, stroke and metabolic disease. The biological mechanisms by which developmental plasticity becomes a risk for cardiovascular disease are only now being understood. Translating from animal and human studies, low birthweight babies are likely to have endothelial dysfunction, fewer nephrons, fewer pancreatic beta cells, less vascular elastin, fewer cardiomyocytes, increased sympathetic tone and liver-derived dyslipidemias. Only in the past few years, however, has it become known that maternal and placenta phenotypes are associated with adult onset cardiovascular disease. Helsinki Birth Cohort studies have been especially important in the discovery of these relationships. Sudden cardiac death is associated with a thin placenta and heart failure is associated with a small placenta in short mothers. Coronary heart disease is associated with three combinations of maternal-placental phenotypes. Because the diet is important in providing nutrients for the development of the female body before pregnancy and for providing nutrients during pregnancy, there is increasing evidence that the western diet is an underlying cause for the increase in metabolic disease in the American population. A large segment of the American population suffers from high calorie malnutrition. Scientists in this field now have a responsibility to educate the public on the topic of nutrition and health. This chapter honors Lawrence Longo for decades of work in bringing health to pregnant women and their babies.
    Advances in Experimental Medicine and Biology 07/2014; 814:205-216. DOI:10.1007/978-1-4939-1031-1_18 · 1.96 Impact Factor
  • Siwen Yang · Wei Li · John R G Challis · Gregor Reid · Sung O Kim · Alan D Bocking ·
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    ABSTRACT: The objective of this study was to determine the effect of probiotic Lactobacillus rhamnosus GR-1 supernatant (GR-1 SN) on lipopolysaccharide (LPS) induced preterm birth (PTB) and outputs of cytokines, chemokines and progesterone in pregnant CD-1 mice. PTB rates following intrauterine injection of LPS with and without prior GR-1 SN treatment were compared. Cytokines and chemokines in the maternal plasma, myometrium, placenta and amniotic fluid were examined with multiplex assay, and circulating maternal progesterone was measured with enzyme-linked immunoassay. Statistical significance was assessed using One-Way Analysis of variance (ANOVA) or ANOVA on ranks. Fetal sex ratios in mice that delivered preterm were compared with those that delivered at term following LPS and GR-1 SN treatments. GR-1 SN reduced LPS-induced PTB by 43%. GR-1 SN significantly decreased the LPS-induced production of IL-1β, IL-6, IL-12p40, TNFα, CCL4 and CCL5 in maternal plasma; IL-6, IL-12p70, TNFα, IL-17 and IL-13 in myometrium; IL-6, IL-12p70, and IL-17 in placenta and IL-6, TNFα, CCL3 and CCL4 in amniotic fluid. Maternal plasma progesterone was significantly reduced following LPS injection with and without GR-1 SN pretreatment. There was no difference in fetal sex ratios between mice that delivered preterm and those that did not after LPS and GR-1 SN treatments. The supernatant of probiotic Lactobacillus rhamnosus GR-1 attenuated LPS-induced inflammation and PTB in vivo. GR-1 SN may confer therapeutic benefits in preventing infection-associated PTB by controlling systemic and intrauterine inflammation.
    American journal of obstetrics and gynecology 01/2014; 211(1). DOI:10.1016/j.ajog.2014.01.029 · 4.70 Impact Factor
  • Wei Li · Siwen Yang · Sung O Kim · Gregor Reid · John R G Challis · Alan D Bocking ·
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    ABSTRACT: The aim of this study was to assess the effects of bacterial lipopolysaccharide (LPS) and Lactobacillus rhamnosus GR-1 supernatant (GR-1SN) on secretion profiles of cytokines, chemokines, and growth factors from primary cultures of human decidual cells. Lipopolysaccharide significantly increased the output of proinflammatory cytokines (interleukin [IL]-1B, IL-2, IL-6, IL-12p70, IL-15, IL-17A, interferon gamma [IFN-γ], and tumor necrosis factor [TNF]); anti-inflammatory cytokines (IL-1RN, IL-4, IL-9, and IL-10); chemokines (IL-8, eotaxin, IFN-inducible protein 10 [IP-10], monocyte chemoattractant protein 1 [MCP-1], macrophage inflammatory protein-1α [MIP-1α], macrophage inflammatory protein-1β [MIP-1β], and regulated on activation normal T cell expressed and secreted [RANTES]); and growth factors (granulocyte colony-stimulating factor [CSF] 3, CSF-2, and vascular endothelial growth factor A [VEGFA]). Lactobacillus rhamnosus GR-1SN alone significantly increased CSF-3, MIP-1α MIP-1β, and RANTES but decreased IL-15 and IP-10 output. The GR-1SN also significantly or partially reduced LPS-induced proinflammatory cytokines TNF, IFN-γ, IL-1β, IL-2 IL-6, IL-12p70, IL-15, IL-17, and IP-10; partially reduced LPS-induced anti-inflammatory cytokines IL-1RN, IL-4 and IL-10, and LPS-induced VEGFA output but did not affect CSF-3, MIP-1α, MIP-1β, MCP-1, IL-8, and IL-9. Our results demonstrate that GR-1SN attenuates the inflammatory responses to LPS by human decidual cells, suggesting its potential role in ameliorating intrauterine infection.
    Reproductive sciences (Thousand Oaks, Calif.) 01/2014; 21(7). DOI:10.1177/1933719113519171 · 2.23 Impact Factor
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    ABSTRACT: Epidemiological data indicate that an adverse maternal environment during pregnancy predisposes offspring to metabolic syndrome with increased obesity, and type 2 diabetes. The mechanisms are still unclear although epigenetic modifications are implicated and the hypothalamus a likely target. We hypothesised that maternal undernutrition around conception (UN) in sheep would lead to epigenetic changes in hypothalamic neurones regulating energy balance in the offspring, up to five years after the maternal insult. We found striking evidence of decreased glucocorticoid receptor (GR) promoter methylation, decreased H3K27 trimethylation and increased H3K9 acetylation in hypothalami from male and female adult offspring of UN mothers. These findings are entirely compatible with the increased GR mRNA and protein observed in the hypothalami. The increased GR predicted the decreased hypothalamic pro-opiomelanocortin expression and increased obesity we observed in the 5 year old adult males. The epigenetic and expression changes in GR were specific to the hypothalamus. Hippocampal GR mRNA and protein were decreased in UN offspring, whereas pituitary GR was altered in a sex-specific manner. In peripheral polymorphonuclear leukocytes there were no changes in GR methylation or protein, indicating that this epigenetic analysis did not predict changes in the brain. Overall, these results suggest that moderate changes in maternal nutrition, around the time of conception, signal life-long and tissue-specific epigenetic alterations in a key gene regulating energy balance in the hypothalamus.
    Endocrinology 09/2013; 154(12). DOI:10.1210/en.2013-1693 · 4.50 Impact Factor
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    ABSTRACT: 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 11β-HSD2) are involved in the complex mechanism of human parturition. The present study examined mRNA expression and activity of membrane 11β-HSD1 and placental 11β-HSD2 in postdate pregnancies according to response of labor induction. In comparison to postdate women who had spontaneous delivery or after induction the non-responders showed significantly low c and high 11β-HSD2 expression and activity These data suggest that disrupted expression and activity of 11β-HSDs may occur in some postdate pregnancies.
    Placenta 09/2013; 34(11). DOI:10.1016/j.placenta.2013.08.011 · 2.71 Impact Factor

  • Placenta 09/2013; 34(9):A91-A92. DOI:10.1016/j.placenta.2013.06.272 · 2.71 Impact Factor

  • Placenta 09/2013; 34(9):A92. DOI:10.1016/j.placenta.2013.06.273 · 2.71 Impact Factor
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    Thorsten Braun · John R Challis · John P Newnham · Deborah M Sloboda ·
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    ABSTRACT: An adverse early life environment is associated with long-term disease consequences. Adversity early in life is hypothesized to elicit developmental adaptations that serve to improve fetal and postnatal survival and prepare the organism for a particular range of postnatal environments. These processes, while adaptive in their nature, may later prove to be maladaptive or disadvantageous if the pre- and postnatal environments are widely discrepant. The exposure of the fetus to elevated levels of either endogenous or synthetic glucocorticoids, is one model of early life adversity that contributes substantially to the propensity of developing disease. Moreover, early life glucocorticoid exposure has direct clinical relevance as synthetic glucocorticoids are routinely used in the management of women at risk of early preterm birth. In this regard, reports of adverse events in human newborns have raised concerns about the safety of glucocorticoid treatment; synthetic glucocorticoids have detrimental effects on fetal growth and development, childhood cognition and long-term behavioural outcomes. Experimental evidence supports a link between prenatal exposure to synthetic glucocorticoids and alterations in fetal development and changes in placental function, and many of these alterations appear to be permanent. Since the placenta is the conduit between the maternal and fetal environments, it is likely that placental function plays a key role in mediating effects of fetal glucocorticoid exposure on HPA axis development and long-term disease risk. Here, we review recent insights into how the placenta responds to changes in the intrauterine glucocorticoid environment and discuss possible mechanisms by which the placenta mediates fetal hypothalamic-pituitary-adrenal development, metabolism, cardiovascular function and reproduction.
    Endocrine reviews 08/2013; 34(6). DOI:10.1210/er.2013-1012 · 21.06 Impact Factor
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    ABSTRACT: Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40–42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.
    04/2013; 4(02). DOI:10.1017/S204017441200075X
  • T Braun · A Husar · J R G Challis · J W Dudenhausen · W Henrich · A Plagemann · D M Sloboda ·
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    ABSTRACT: Betamethasone (BET) is a widely used treatment for women who are at high risk of preterm delivery. In sheep, BET-induced growth restriction was found to be associated with reduced placenta lactogen (PL), a key regulator of fetal growth. We therefore hypothesized that also in humans a single course of BET administration is associated with a reduction of PL, associated with a deceleration in fetal growth. OBJECTIVE: To investigate effects of a single course of antenatal BET in humans on birth weight and PL. METHODS: Women exposed to BET (2 × 12 mg; n = 44) with normally grown fetuses between 23 + 5 and 34 + 0 wks (weeks + days of gestation) who delivered between 23 + 5 to 42 + 0 wks were compared to gestational age-matched controls (n = 49). Maternal gestational blood samples were obtained before, during and after BET treatment and at the time of birth. MAIN OUTCOME MEASURES: BET effects on fetal anthropometrics, placental morphometry and placental PL-protein and maternal plasma levels. RESULTS: The mean duration of days between BET administration and birth was 52 days. BET treatment was associated with decreased birth weight (-18.2%), head circumference (-8.6%), body length (-6.0%), and placental width (-5.5%), as compared to controls. These changes were irrespective of possible maternal confounders (gestational age at birth, maternal age, maternal BMI gain during pregnancy, smoking etc.). However, neither PL-plasma levels within 48 h after BET treatment nor placental PL-protein levels and maternal plasma levels at birth were changed after BET treatment. In central regions of the placenta, BET treatment increased the circumference of syncytiotrophoblast nuclei by +4.7% and nucleus surface area by +9.4% compared to controls, but these changes were not related to placental PL-protein or maternal PL-plasma levels at birth. CONCLUSION: A single course of BET treatment was accompanied with reduced fetal growth, but this growth restricting effect was not associated with altered placental or maternal plasma PL levels. Altered expression of PL appears not to be causal for BET-induced fetal growth restriction in the human.
    Placenta 03/2013; 34(5). DOI:10.1016/j.placenta.2013.02.002 · 2.71 Impact Factor
  • S. W. Yang · W. Li · J. R. G. Challis · G. Reid · G. B. Gloor · A. D. Bocking ·

    60th Annual Scientific Meeting of the; 03/2013
  • S. W. Yang · W. Li · J. R. G. Challis · G. Reid · S. O. Kim · A. D. Bocking ·

    60th Annual Scientific Meeting of the; 03/2013

  • 03/2013; DOI:10.1530/endoabs.31.OC4.3

  • 60th Annual Scientific Meeting of the; 03/2013
  • Source
    S. Li · T. J. M. Moss · I. Nitsos · S. G. Matthews · J. R. G. Challis · J. P. Newnham · D. M. Sloboda ·
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    ABSTRACT: In this study, we determined the gene and/or protein expression of hypothalamic–pituitary–adrenal (HPA) axis regulatory molecules following synthetic glucocorticoid exposures. Pregnant sheep received intramuscular saline or betamethasone (BET) injections at 104 (BET-1), 104 and 111(BET-2) or 104, 111 and 118 (BET-3) days of gestation (dG). Samples were collected at numerous time-points between 75 dG and 12 weeks postnatal age. In the BET-3 treatment group, fetal plasma cortisol levels were lower at 145 dG than controls and gestational length was lengthened significantly. The cortisol:adrenocorticotropic hormone (ACTH) ratio in fetal plasma of control and BET-3 fetuses rose significantly between132 and 145 dG, and remained elevated in lambs at 6 and 12 weeks of age; this rise was truncated at day 145 in fetuses of BET-3 treated mothers. After BET treatment, fetal and postnatal pituitary proopiomelanocortin mRNA levels were reduced from 109 dG to 12 weeks postnatal age; pituitary prohormone convertase 1 and 2 mRNA levels were reduced at 145 dG and postnatally; hypothalamic arginine vasopressin mRNA levels were lowered at all time-points, but corticotrophin-releasing hormone mRNA levels were reduced only in postnatal lambs. Maternal BET increased late fetal and/or postnatal adrenal mRNA levels of ACTH receptor and 3β hydroxysteroid dehydrogenase but decreased steroidogenic acute regulatory protein and P450 17-α hydroxylase. The altered mRNA levels of key HPA axis regulatory proteins after maternal BET injections suggests processes that may subserve long-term changes in HPA activity in later life after prenatal exposure to synthetic glucocorticoids.
    02/2013; 4(01). DOI:10.1017/S2040174412000591
  • J Challis · J Newnham · F Petraglia · M Yeganegi · A Bocking ·
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    ABSTRACT: Rates of preterm birth vary between different populations and ethnic groups. Epidemiologic studies have suggested that the incidence of preterm birth is also higher in pregnancies carrying a male fetus; the male:female difference is greater in earlier preterm pregnancy. Placental or chorion trophoblast cells from pregnancies with a male fetus produced more pro-inflammatory TNFα in response to LPS stimulation and less anti-inflammatory IL-10 and granulocyte colony stimulating factor (G-CSF) than cells from pregnancies with a female fetus, more prostaglandin synthase (PTGS-2) and less prostaglandin dehydrogenase (PGDH). These results suggest that in the presence of a male fetus the trophoblast has the potential to generate a more pro-inflammatory environment. Maturation of the fetal hypothalamic-pituitary-adrenal axis and expression of placental genes, particularly 11β hydroxysteroid dehydrogenase-2 are also expressed in a sex dependent manner, consistent with the sex-biasing influences on gene networks. Sex differences in these activities may affect clinical outcomes of pre- and post-dates pregnancies and fetal/newborn wellbeing. These factors need consideration in studies of placental function and in the development of personalized strategies for the diagnosis of preterm labor and postnatal health.
    Placenta 12/2012; 34(2). DOI:10.1016/j.placenta.2012.11.007 · 2.71 Impact Factor

Publication Stats

12k Citations
1,741.33 Total Impact Points


  • 2012-2015
    • Simon Fraser University
      • Faculty of Health Sciences
      Burnaby, British Columbia, Canada
  • 1996-2015
    • University of Toronto
      • • Department of Obstetrics and Gynaecology
      • • Department of Physiology
      • • Faculty of Medicine
      Toronto, Ontario, Canada
  • 2002-2013
    • University of Western Australia
      • School of Women's and Infants' Health
      Perth City, Western Australia, Australia
  • 2010-2011
    • Università degli Studi di Siena
      • Department of Molecular & Developmental Medicine
      Siena, Tuscany, Italy
  • 1979-2010
    • The University of Western Ontario
      • • Department of Obstetrics and Gynaecology
      • • Department of Medicine
      London, Ontario, Canada
    • McMaster University
      Hamilton, Ontario, Canada
  • 2009
    • Michael Smith Foundation for Health Research
      Vancouver, British Columbia, Canada
  • 2007
    • Mount Sinai Hospital, Toronto
      • Department of Obstetrics and Gynecology
      Toronto, Ontario, Canada
    • The University of Manchester
      Manchester, England, United Kingdom
  • 2004-2007
    • Samuel Lunenfeld Research Institute
      Toronto, Ontario, Canada
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1989-2005
    • Lawson Health Research Institute
      London, Ontario, Canada
  • 1996-2002
    • University of Ottawa
      • Department of Obstetrics and Gynecology
      Ottawa, Ontario, Canada
  • 2000
    • Catholic University of the Sacred Heart
      • School of Obstetrics and Gynecology
      Milano, Lombardy, Italy
  • 1987-1999
    • St. Joseph's Health Care London
      London, Ontario, Canada
  • 1998
    • Sapienza University of Rome
      • Department of Gynecology-Obstetrics & Urology
      Roma, Latium, Italy
  • 1997
    • Leiden University Medical Centre
      Leyden, South Holland, Netherlands
  • 1991
    • Lawson Health Research Institute
      Guilford, England, United Kingdom
  • 1985-1989
    • Government of Ontario, Canada
      XIA, Ontario, Canada
  • 1986
    • St. Joseph's Hospital
      Savannah, Georgia, United States
  • 1977
    • McGill University
      Montréal, Quebec, Canada
  • 1976-1977
    • Oxford University Hospitals NHS Trust
      • Department of Obstetrics and Gynaecology
      Oxford, England, United Kingdom
  • 1975-1977
    • University of Oxford
      • Nuffield Department of Obstetrics and Gynaecology
      Oxford, ENG, United Kingdom
  • 1973-1974
    • Harvard Medical School
      Boston, Massachusetts, United States