In Utero Exposure to Environmentally Relevant Concentrations of PCB 153 and PCB 118 Disrupts Fetal Testis Development in Sheep

Anette K Krogenæs, Erik Ropstad, Arno C Gutleb, Nina Hårdnes, Vidar Berg, Ellen Dahl, Paul A Fowler

Research output: Contribution to journalArticle

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Abstract

Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)-mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production.
Original languageEnglish
Pages (from-to)628-649
Number of pages22
JournalJournal of Toxicology and Environmental Health. Part A
Volume77
Issue number9-11
DOIs
Publication statusPublished - 2014

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Polychlorinated Biphenyls
Fetal Development
Testis
Sheep
Testosterone
Seminiferous Tubules
Proteome
Proteomics
Mass Spectrometry
Body Weight
Spectroscopy
Environmental Pollutants
Euthanasia
Sertoli Cells
Liquid chromatography
Heat-Shock Proteins
Cytoskeleton
Fetal Blood
Liquid Chromatography

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In Utero Exposure to Environmentally Relevant Concentrations of PCB 153 and PCB 118 Disrupts Fetal Testis Development in Sheep. / Krogenæs, Anette K; Ropstad, Erik; Gutleb, Arno C; Hårdnes, Nina; Berg, Vidar; Dahl, Ellen; Fowler, Paul A.

In: Journal of Toxicology and Environmental Health. Part A, Vol. 77, No. 9-11, 2014, p. 628-649.

Research output: Contribution to journalArticle

Krogenæs, Anette K ; Ropstad, Erik ; Gutleb, Arno C ; Hårdnes, Nina ; Berg, Vidar ; Dahl, Ellen ; Fowler, Paul A. / In Utero Exposure to Environmentally Relevant Concentrations of PCB 153 and PCB 118 Disrupts Fetal Testis Development in Sheep. In: Journal of Toxicology and Environmental Health. Part A. 2014 ; Vol. 77, No. 9-11. pp. 628-649.
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title = "In Utero Exposure to Environmentally Relevant Concentrations of PCB 153 and PCB 118 Disrupts Fetal Testis Development in Sheep",
abstract = "Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)-mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production.",
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AU - Berg, Vidar

AU - Dahl, Ellen

AU - Fowler, Paul A

N1 - This work was supported by the Research Council of Norway (158849). The authors are grateful to Margaret Fraser, Evelyn Argo, and Elizabeth Stewart (University of Aberdeen) for their excellent technical assistance with the gels and proteomic analyses. We also thank Mona Aleksandersen, Tore Engen, Jens Røhnebæk, and Camilla Almås for valuable technical assistance with animals and tissue preparation and Gjermund Gunnes for guiding in the morphometric studies.

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N2 - Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)-mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production.

AB - Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)-mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production.

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