The fetal ovary exhibits temporal sensitivity to a 'real-life' mixture of environmental chemicals.

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

doi:10.1038/srep22279

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.

Highlights

The development of fetal ovarian follicles is a critical determinant of adult female reproductive competence
The deleterious effects of exposure to environmental chemicals (ECs), including endocrine disrupting compounds (EDCs), on female reproductive function have been demonstrated in diverse species[1,2], especially at immature life stages[3,4]
We have reported that prolonged use of sewage sludge fertilizer increases the soil content of many ECs/EDCs11

Summary

Introduction

The development of fetal ovarian follicles is a critical determinant of adult female reproductive competence. We previously subjected pregnant ewes to a complex mixture of ECs for a prolonged period by grazing pastures fertilized with sewage sludge (biosolids); a common agricultural practice. This valuable fertilizer contains readily detectable levels of EDCs7–10 which, through release into the environment, represents animal and human exposure. Fetal hypothalamo-pituitary function develops after 60 dpc[20], and by 140 days the first antral follicles are present[21], with birth at 145–150 dpc Using this model we establish the gestational periods during which the fetal ovary is most sensitive to perturbation by a complex, low dose, mixture of ECs

Methods

Results

Conclusion