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

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


Professor of Reproductive Biology

Maria R. Amezaga

Benoit Loup

B�atrice Mandon- P�pin

Agnes Stefansdottir

Panagiotis Filis

Carol Kyle

Zulin Zhang

Ceri Allen

Laura Purdie

Luc Jouneau

Corinne Cotinot

Stewart M. Rhind

Professor of Developmental Biology

Paul A. Fowler


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.


Lea, R. G., Amezaga, M. R., Loup, B., Mandon- Pépin, B., Stefansdottir, A., Filis, P., …Fowler, P. . A. (2016). The fetal ovary exhibits temporal sensitivity to a ‘real-life’ mixture of environmental chemicals. Scientific Reports, 6, 22279.

Journal Article Type Article
Acceptance Date Feb 10, 2016
Online Publication Date Mar 2, 2016
Publication Date Mar 2, 2016
Deposit Date Nov 19, 2018
Publicly Available Date Jan 21, 2019
Journal Scientific Reports
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 6
Pages 22279
Public URL
Publisher URL


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