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.
authors.affiliation: a Department of Production Animal Sciences , Norwegian School Veterinary Science , Oslo , Norway.
authors.forename: Anette K
authors.initials: AK
authors.lastname: Krogenæs
authors.forename: Erik
authors.initials: E
authors.lastname: Ropstad
authors.forename: Arno C
authors.initials: AC
authors.lastname: Gutleb
authors.forename: Nina
authors.initials: N
authors.lastname: Hårdnes
authors.forename: Vidar
authors.initials: V
authors.lastname: Berg
authors.forename: Ellen
authors.initials: E
authors.lastname: Dahl
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fowler
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D040901:Proteomics; D012671:Seminiferous Tubules / Q000187:drug effects / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism; D012756:Sheep / Q000196:embryology*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; C070055:2,3',4,4',5-pentachlorobiphenyl; D013739:Testosterone; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl