Developmental exposure to real-life environmental chemical mixture programs a testicular dysgenesis syndrome-like phenotype in prepubertal lambs

Elcombe, C. S., Monteiro, A., Elcombe, M. R., Ghasemzadeh-Hasankolaei, M., Sinclair, K. D., Lea, R., Padmanabhan, V., Evans, N. P. and Bellingham, M. (2022) Developmental exposure to real-life environmental chemical mixture programs a testicular dysgenesis syndrome-like phenotype in prepubertal lambs. Environmental Toxicology and Pharmacology, 94, 103913. (doi: 10.1016/j.etap.2022.103913) (PMID:35738462)

Abstract

Current declines in male reproductive health may, in part, be driven by anthropogenic environmental chemical (EC) exposure. Using a biosolids treated pasture (BTP) sheep model, this study examined the effects of gestational exposure to a translationally relevant EC mixture. Testes of 8-week-old ram lambs from mothers exposed to BTP during pregnancy contained fewer germ cells and had a greater proportion of Sertoli-cell-only seminiferous tubules. This concurs with previous published data from fetuses and neonatal lambs from mothers exposed to BTP. Comparison between the testicular transcriptome of biosolids lambs and human testicular dysgenesis syndrome (TDS) patients indicated common changes in genes involved in apoptotic and mTOR signalling. Gene expression data and immunohistochemistry indicated increased HIF1α activation and nuclear localisation in Leydig cells of BTP exposed animals. As HIF1α is reported to disrupt testosterone synthesis, these results provide a potential mechanism for the pathogenesis of this testicular phenotype, and TDS in humans.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bellingham, Dr Michelle and Ghasemzadeh Hasankolaei, Dr Mohammad and Monteiro, Dr Ana and Elcombe, Mr Chris and Evans, Professor Neil

Creator Roles

Elcombe, C. S.: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing – original draft
Monteiro, A.: Methodology, Investigation
Ghasemzadeh-Hasankolaei, M.: Writing – review and editing
Evans, N. P.: Conceptualization, Methodology, Writing – review and editing, Supervision
Bellingham, M.: Conceptualization, Project administration, Writing – review and editing, Supervision

• Authors: Elcombe, C. S., Monteiro, A., Elcombe, M. R., Ghasemzadeh-Hasankolaei, M., Sinclair, K. D., Lea, R., Padmanabhan, V., Evans, N. P., and Bellingham, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Environmental Toxicology and Pharmacology
• Publisher: Elsevier
• ISSN: 1382-6689
• ISSN (Online): 1872-7077
• Published Online: 20 June 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Environmental Toxicology and Pharmacology 94: 103913
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302571		Transgenerational consequences of pre-conceptional and in utero exposure to real-life chemical mixtures on fertility and metabolic health	Neil Evans	National Institutes of Health (NIH)	1 R01 ES030374-01A1	Institute of Biodiversity, Animal Health and Comparative Medicine