Timing of maternal exposure and fetal sex determine the effects of low-level chemical mixture exposure on the fetal neuroendocrine system in sheep

Bellingham, M., Fowler, P.A., MacDonald, E.S., Mandon-Pepin, B., Cotinot, C., Rhind, S., Sharpe, R.M. and Evans, N.P. (2016) Timing of maternal exposure and fetal sex determine the effects of low-level chemical mixture exposure on the fetal neuroendocrine system in sheep. Journal of Neuroendocrinology, 28(12), 12444. (doi:10.1111/jne.12444) (PMID:27870155)

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Abstract

We have shown that continuous maternal exposure to the complex mixture of environmental chemicals (ECs) found in human biosolids (sewage sludge), disrupts mRNA expression of genes crucial for development and long-term regulation of hypothalamo-pituitary gonadal (HPG) function in sheep. This study investigated whether exposure to ECs only during preconceptional period or only during pregnancy perturbed key regulatory genes within the hypothalamus and pituitary gland and whether these effects were different from chronic (life-long) exposure to biosolid ECs. The findings demonstrate that the timing and duration of maternal EC exposure influences the subsequent effects on the fetal neuroendocrine system in a sex-specific manner. Maternal exposure prior to conception or during pregnancy only, altered the expression of key fetal neuroendocrine regulatory systems such as GnRH and kisspeptin to a greater extent than when maternal exposure was ‘life-long’. Furthermore, hypothalamic gene expression was affected to a greater extent in males than in females, and following EC exposure, male fetuses expressed more “female-like” mRNA levels for some key neuroendocrine genes. This is the first study to show that “real-life” maternal exposure to low levels of a complex cocktail of chemicals prior to conception can subsequently affect the developing fetal neuroendocrine system. These findings demonstrate that the developing neuroendocrine system is sensitive to EC mixtures in a sex-dimorphic manner likely to predispose to reproductive dysfunction in later life.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bellingham, Dr Michelle and Evans, Professor Neil and Rhind, Dr Susan
Authors: Bellingham, M., Fowler, P.A., MacDonald, E.S., Mandon-Pepin, B., Cotinot, C., Rhind, S., Sharpe, R.M., and Evans, N.P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Journal of Neuroendocrinology
Publisher:Wiley
ISSN:0953-8194
ISSN (Online):1365-2826
Published Online:21 November 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Journal of Neuroendocrinology 28(12):12444
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
419423Effects of in-utero exposure to environmental chemicals via maternal pasture ingestion on fetal ovine reproductive developmentNeil EvansWellcome Trust (WELLCOME)080388/Z/06/ZRI BIODIVERSITY ANIMAL HEALTH & COMPMED