title: The fetal ovary exhibits temporal sensitivity to a 'real-life' mixture of environmental chemicals.
abstract: The development of fetal ovarian follicles is a critical determinant of adult female reproductive competence. Prolonged exposure to environmental chemicals (ECs) can perturb this process with detrimental consequences for offspring. Here we report on the exposure of pregnant ewes to an environmental mixture of ECs derived from pastures fertilized with sewage sludge (biosolids): a common global agricultural practice. Exposure of pregnant ewes to ECs over 80 day periods during early, mid or late gestation reduced the proportion of healthy early stage fetal follicles comprising the ovarian reserve. Mid and late gestation EC exposures had the most marked effects, disturbing maternal and fetal liver chemical profiles, masculinising fetal anogenital distance and greatly increasing the number of altered fetal ovarian genes and proteins. In conclusion, differential temporal sensitivity of the fetus and its ovaries to EC mixtures has implications for adult ovarian function following adverse exposures during pregnancy.
authors.affiliation: Schools of Veterinary Medicine and Biosciences, University of Nottingham, Leicestershire, LE12 5RD, UK.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Lea
authors.affiliation: Institute of Medical Sciences, School of Medicine, Medical Sciences &Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Amezaga
authors.affiliation: UMR BDR, INRA, Université Paris Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Loup
authors.affiliation: UMR BDR, INRA, Université Paris Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Mandon-Pépin
authors.affiliation: Institute of Medical Sciences, School of Medicine, Medical Sciences &Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
authors.forename: Agnes
authors.initials: A
authors.lastname: Stefansdottir
authors.affiliation: Institute of Medical Sciences, School of Medicine, Medical Sciences &Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Filis
authors.affiliation: The James Hutton Institute, Craigiebuckler, Aberdeen, AB15 8QH, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Kyle
authors.affiliation: The James Hutton Institute, Craigiebuckler, Aberdeen, AB15 8QH, UK.
authors.forename: Zulin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Schools of Veterinary Medicine and Biosciences, University of Nottingham, Leicestershire, LE12 5RD, UK.
authors.forename: Ceri
authors.initials: C
authors.lastname: Allen
authors.affiliation: Schools of Veterinary Medicine and Biosciences, University of Nottingham, Leicestershire, LE12 5RD, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Purdie
authors.affiliation: UMR BDR, INRA, Université Paris Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Jouneau
authors.affiliation: UMR BDR, INRA, Université Paris Saclay, 78350, Jouy-en-Josas, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Cotinot
authors.affiliation: The James Hutton Institute, Craigiebuckler, Aberdeen, AB15 8QH, UK.
authors.forename: Stewart M
authors.initials: SM
authors.lastname: Rhind
authors.affiliation: Schools of Veterinary Medicine and Biosciences, University of Nottingham, Leicestershire, LE12 5RD, UK.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Sinclair
authors.affiliation: Institute of Medical Sciences, School of Medicine, Medical Sciences &Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fowler
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D018811:Maternal Exposure; D009687:Nuclear Proteins / Q000378:metabolism; D006080:Ovarian Follicle / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D011247:Pregnancy; D021381:Protein Transport / Q000187:drug effects; D020543:Proteome / Q000378:metabolism; D012722:Sewage / Q000737:chemistry; D012756:Sheep / Q000196:embryology / Q000235:genetics; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D004785:Environmental Pollutants; D007797:Laminin; D009687:Nuclear Proteins; D020543:Proteome; D012722:Sewage