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.

doi:10.1038/srep22279

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.

Authors

RICHARD LEA richard.lea@nottingham.ac.uk
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

KEVIN SINCLAIR kevin.sinclair@nottingham.ac.uk
Professor of Developmental Biology

Paul A. Fowler

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.

Citation

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. https://doi.org/10.1038/srep22279

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
DOI	https://doi.org/10.1038/srep22279
Public URL	https://nottingham-repository.worktribe.com/output/1285947
Publisher URL	https://www.nature.com/articles/srep22279