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)
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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 |
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