The fetal ovary exhibits temporal sensitivity to a ‘real-life’ mixture of environmental chemicals

Richard G. Lea, Maria R. Amezaga, Benoit Loup, Beatrice Mandon-Pepin, Agnes Stefansdottir, Panagiotis Filis, Carol Kyle, Zulin Zhang, Ceri Allen, Laura Purdie, Luc Jouneau, Corinne Cotinot, Stewart M. Rhind, Kevin D. Sinclair, Paul A. Fowler

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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.
Original languageEnglish
Article number22279
Number of pages13
JournalScientific Reports
Publication statusPublished - 2 Mar 2016

Bibliographical note

We thank George Corsar and Jim MacDonald for the management of experimental animals. We thank Ms Evelyn Argo, Mr Ian Davidson (Proteomics Facility), Ms Gillian Milne (Histology & Electron Microscopy Facility) and Mrs Margaret Fraser (Institute of Medical Sciences) at the University of Aberdeen and NHS Grampian for expert technical assistance. We thank Elodie Poumerol (UMR1198 INRA, transcriptome analysis), Christine Kerr and Mark Osprey (James Hutton Institute, chemical analysis) for technical support. This work was funded by the European Commission Framework 7 Programme (Contract No 212885,


  • Developmental biology
  • Embryology


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