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Lifestyle and fertility: how pesticides and cafeteria diet affects the uterine development and female fertility
108
Abstracts / Placenta 51 (2017) 98e131
Objective: The objective of this study was to examine the molecular mechanisms involved on the development and function of the endocrine pancreas postnatally when olive oil was supplemented to the diets of T1D mothers or a westernized diet rich in fats and fructose was given to an intrauterine restriction model with uterine ligation. Methods: Morphometric and gene expression of PPARs and target genes involved in the differentiation of b-cells were analysed. Results: the addition of olive oil to dams rescued the offspring from insulin resistance meanwhile the westernized diet increased this predisposition at 4 months. Conclusions: Individual customized dietary intervention is needed during pregnancy to reduce the burden of metabolic disease.
http://dx.doi.org/10.1016/j.placenta.2017.01.039
INSIGHT INSIDE: IMAGING FETAL ADIPOSE TISSUE DEVELOPMENT WITH 3D WATER-FAT MRI B. de Vrijer, S. Giza, C. Olmstead, D. Penava, G. Eastabrook, T.R.H. Regnault, C.A. McKenzie. Western University, London, Ontario, Canada Infants born small (SGA) or large for gestational age (LGA) and after pregnancies complicated by maternal diabetes have increased risk of mortality and morbidity promoting future obesity and metabolic disease. In SGA, this is likely the result of a nutritional mismatch before and after birth, while excess storage and increased availability of nutrients appears to be the pathophysiology in LGA offspring; resulting in promotion of adipose tissue development in both situations. Objective: We sought to investigate abnormal fetal fat development indicative of future metabolic health risk in vivo using a novel MRI technique. Methods: 3D water-fat MRI, a technique sensitive to the lipid content of tissues, was used to assess the transition from water-filled pre-adipocytes into mature fat-filled adipocytes in fetal subcutaneous adipose tissue (FSAT). 3D water-fat MRI provides a fat fraction (FF ¼ fat/(water + fat)) that quantifies the proportion of MRI signal received from lipid. Results: In pregnancies with gestational ages between 28 and 38 weeks, we found no correlation between FF or lipid volume and maternal pre-pregnancy BMI or EFW percentile, but observed a significant positive correlation between FF and lipid volume and gestational age. We describe the distribution and maturation of FSAT in normal, obese and diabetic pregnancies. Conclusion: 3D water-fat MRI can be used to non-invasively study fetal adipose tissue development in mid- to late gestation, a crucial developmental stage during which adipocytes rapidly fill with lipid. This technique can improve our understanding of fetal metabolic health in pregnancies complicated with diabetes, obesity and abnormal fetal growth. http://dx.doi.org/10.1016/j.placenta.2017.01.040
S9 FRONTIERS IN MATERNAL-FOETAL RESEARCH. EHMT2/G9A CONTROLS VASCULATURE
MATURATION
OF
THE
PLACENTAL
L. Chi 1, A. Ahmed 1,2, A.R. Roy 1, 2, S. Vuong 1, 2, L.S. Cahill 1, L. Caporiccio 1, J.G. Sled 1, I. Caniggia 3, M.D. Wilson 1, 2, P. Delgado-Olguin 1, 2. 1
The Hospital for Sick Children, Toronto, Canada; 2 Department of Molecular Genetics, University of Toronto, Canada; 3 Mount Sinai Hospital, Toronto, Canada G9a is an epigenetic regulator controlling embryogenesis; however, its function in the cellular processes and molecular pathways
controlling placental vascular maturation and placental disease are unknown. Objective: To uncover the function of G9a in maturation of the placental vasculature, and its involvement in placental disease. Methods: Extension and structure of the placental vasculature, and proliferation of endothelial cells and trophoblasts were quantified in endothelial-specific G9a mutant mice. Genomewide expression analysis and a genetic rescue uncovered the main G9a target pathway. Expression of human G9A and its main targets was analyzed in placentae from pregnancies affected by intrauterine growth restriction (IUGR). Results: Decreased proliferation of endothelial cells (35 ± 9%) (P<0.01, n ¼ 4), concomitant with increased proliferation of trophoblasts (2.5 ± 0.4 fold) (P<0.01, n ¼ 4) prevented vascular expansion in maturing G9a mutant placentae. In addition, genes encoding proteins in the Notch pathway were downregulated in G9a mutant placental endothelial cells. Moreover, constitutive activation of the Notch pathway in G9a mutant endothelial cells restored expansion of the placental vasculature. Furthermore, G9A and proteins in the Notch pathway were decreased in placentae from human pregnancies affected by IUGR. Conclusion: G9a-mediated activation of the Notch pathway in endothelial cells is required for placental vascular maturation. We are testing whether pharmacologic activation of the Notch pathway promotes placental vascular maturation.
http://dx.doi.org/10.1016/j.placenta.2017.01.051
LIFESTYLE AND FERTILITY: HOW PESTICIDES AND CAFETERIA DIET AFFECTS THE UTERINE DEVELOPMENT AND FEMALE FERTILITY J. Varayoud, M.M. Milesi, P.I. Ingaramo, M. Guerrero Schimpf, M.P. Gastiazoro, M.V. Zanardi, M. Durando, V. Lorenz, J.G. Ramos, E.H. Luque. Institute of Health and Environment of Litoral (ISAL), Faculty of Biochemistry and Biological Sciences, Universidad Nacional del Litoral e Consejo Nacional de Investigaciones Científicas y T ecnicas, Santa Fe, Argentina Infertility affects up to 15% of reproductive-aged couples worldwide. Evidence is mounting that lifestyle factors, such as exposure to chemicals and diet, affect uterine functions and may contribute to infertility. We evaluate the consequences of cafeteria diet and pesticide exposure on uterine development and female fertility. Using a rat model we observed that low doses of endosulfan and low doses of a glyphosate-based herbicide disrupt the expression of genes that regulate uterine development and differentiation during the pre-pubertal period. In addition, we studied long-term effects of pesticides and cafeteria diet on reproductive performance and implantation and post-implantation processes. Both pesticides affected female fertility, but in different ways. Low doses of endosulfan decreased the number of implantation sites. In the case of the glyphosate-based herbicide, there is an increased number of resorption sites. To address the effects of postnatal pesticide exposure on the pregnant uterus, we evaluated the endometrial proliferation and the expression of implantation and decidualization-associated genes. Both pesticides impaired endometrial proliferation and altered the expression of endocrine-regulated gene pathways. The cafeteria diet did not produce subfertility but the foetal growth and placental development were altered. In addition, we found epigenetic modifications associated with the alteration of uterine gene expression. Based on the evidence presented here and previously published data, we conclude that some pesticides and cafeteria diet are likely to diminish fertility in a laboratory animal model. More studies are needed to identify that these lifestyle factors may contribute to the decline in human fertility observed in the past decades.
http://dx.doi.org/10.1016/j.placenta.2017.01.041
Abstracts / Placenta 51 (2017) 98e131
Objective: The objective of this study was to examine the molecular mechanisms involved on the development and function of the endocrine pancreas postnatally when olive oil was supplemented to the diets of T1D mothers or a westernized diet rich in fats and fructose was given to an intrauterine restriction model with uterine ligation. Methods: Morphometric and gene expression of PPARs and target genes involved in the differentiation of b-cells were analysed. Results: the addition of olive oil to dams rescued the offspring from insulin resistance meanwhile the westernized diet increased this predisposition at 4 months. Conclusions: Individual customized dietary intervention is needed during pregnancy to reduce the burden of metabolic disease.
http://dx.doi.org/10.1016/j.placenta.2017.01.039
INSIGHT INSIDE: IMAGING FETAL ADIPOSE TISSUE DEVELOPMENT WITH 3D WATER-FAT MRI B. de Vrijer, S. Giza, C. Olmstead, D. Penava, G. Eastabrook, T.R.H. Regnault, C.A. McKenzie. Western University, London, Ontario, Canada Infants born small (SGA) or large for gestational age (LGA) and after pregnancies complicated by maternal diabetes have increased risk of mortality and morbidity promoting future obesity and metabolic disease. In SGA, this is likely the result of a nutritional mismatch before and after birth, while excess storage and increased availability of nutrients appears to be the pathophysiology in LGA offspring; resulting in promotion of adipose tissue development in both situations. Objective: We sought to investigate abnormal fetal fat development indicative of future metabolic health risk in vivo using a novel MRI technique. Methods: 3D water-fat MRI, a technique sensitive to the lipid content of tissues, was used to assess the transition from water-filled pre-adipocytes into mature fat-filled adipocytes in fetal subcutaneous adipose tissue (FSAT). 3D water-fat MRI provides a fat fraction (FF ¼ fat/(water + fat)) that quantifies the proportion of MRI signal received from lipid. Results: In pregnancies with gestational ages between 28 and 38 weeks, we found no correlation between FF or lipid volume and maternal pre-pregnancy BMI or EFW percentile, but observed a significant positive correlation between FF and lipid volume and gestational age. We describe the distribution and maturation of FSAT in normal, obese and diabetic pregnancies. Conclusion: 3D water-fat MRI can be used to non-invasively study fetal adipose tissue development in mid- to late gestation, a crucial developmental stage during which adipocytes rapidly fill with lipid. This technique can improve our understanding of fetal metabolic health in pregnancies complicated with diabetes, obesity and abnormal fetal growth. http://dx.doi.org/10.1016/j.placenta.2017.01.040
S9 FRONTIERS IN MATERNAL-FOETAL RESEARCH. EHMT2/G9A CONTROLS VASCULATURE
MATURATION
OF
THE
PLACENTAL
L. Chi 1, A. Ahmed 1,2, A.R. Roy 1, 2, S. Vuong 1, 2, L.S. Cahill 1, L. Caporiccio 1, J.G. Sled 1, I. Caniggia 3, M.D. Wilson 1, 2, P. Delgado-Olguin 1, 2. 1
The Hospital for Sick Children, Toronto, Canada; 2 Department of Molecular Genetics, University of Toronto, Canada; 3 Mount Sinai Hospital, Toronto, Canada G9a is an epigenetic regulator controlling embryogenesis; however, its function in the cellular processes and molecular pathways
controlling placental vascular maturation and placental disease are unknown. Objective: To uncover the function of G9a in maturation of the placental vasculature, and its involvement in placental disease. Methods: Extension and structure of the placental vasculature, and proliferation of endothelial cells and trophoblasts were quantified in endothelial-specific G9a mutant mice. Genomewide expression analysis and a genetic rescue uncovered the main G9a target pathway. Expression of human G9A and its main targets was analyzed in placentae from pregnancies affected by intrauterine growth restriction (IUGR). Results: Decreased proliferation of endothelial cells (35 ± 9%) (P<0.01, n ¼ 4), concomitant with increased proliferation of trophoblasts (2.5 ± 0.4 fold) (P<0.01, n ¼ 4) prevented vascular expansion in maturing G9a mutant placentae. In addition, genes encoding proteins in the Notch pathway were downregulated in G9a mutant placental endothelial cells. Moreover, constitutive activation of the Notch pathway in G9a mutant endothelial cells restored expansion of the placental vasculature. Furthermore, G9A and proteins in the Notch pathway were decreased in placentae from human pregnancies affected by IUGR. Conclusion: G9a-mediated activation of the Notch pathway in endothelial cells is required for placental vascular maturation. We are testing whether pharmacologic activation of the Notch pathway promotes placental vascular maturation.
http://dx.doi.org/10.1016/j.placenta.2017.01.051
LIFESTYLE AND FERTILITY: HOW PESTICIDES AND CAFETERIA DIET AFFECTS THE UTERINE DEVELOPMENT AND FEMALE FERTILITY J. Varayoud, M.M. Milesi, P.I. Ingaramo, M. Guerrero Schimpf, M.P. Gastiazoro, M.V. Zanardi, M. Durando, V. Lorenz, J.G. Ramos, E.H. Luque. Institute of Health and Environment of Litoral (ISAL), Faculty of Biochemistry and Biological Sciences, Universidad Nacional del Litoral e Consejo Nacional de Investigaciones Científicas y T ecnicas, Santa Fe, Argentina Infertility affects up to 15% of reproductive-aged couples worldwide. Evidence is mounting that lifestyle factors, such as exposure to chemicals and diet, affect uterine functions and may contribute to infertility. We evaluate the consequences of cafeteria diet and pesticide exposure on uterine development and female fertility. Using a rat model we observed that low doses of endosulfan and low doses of a glyphosate-based herbicide disrupt the expression of genes that regulate uterine development and differentiation during the pre-pubertal period. In addition, we studied long-term effects of pesticides and cafeteria diet on reproductive performance and implantation and post-implantation processes. Both pesticides affected female fertility, but in different ways. Low doses of endosulfan decreased the number of implantation sites. In the case of the glyphosate-based herbicide, there is an increased number of resorption sites. To address the effects of postnatal pesticide exposure on the pregnant uterus, we evaluated the endometrial proliferation and the expression of implantation and decidualization-associated genes. Both pesticides impaired endometrial proliferation and altered the expression of endocrine-regulated gene pathways. The cafeteria diet did not produce subfertility but the foetal growth and placental development were altered. In addition, we found epigenetic modifications associated with the alteration of uterine gene expression. Based on the evidence presented here and previously published data, we conclude that some pesticides and cafeteria diet are likely to diminish fertility in a laboratory animal model. More studies are needed to identify that these lifestyle factors may contribute to the decline in human fertility observed in the past decades.
http://dx.doi.org/10.1016/j.placenta.2017.01.041