Developmental exposure to a real-life environmental chemical mixture alters testicular transcription factor expression in neonatal and pre-pubertal rams, with morphological changes persisting into adulthood

Elcombe, C. S., Monteiro, A., Ghasemzadeh-Hasankolaei, M., Padmanabhan, V., Lea, R., Sinclair, K. D., Evans, N. P. and Bellingham, M. (2023) Developmental exposure to a real-life environmental chemical mixture alters testicular transcription factor expression in neonatal and pre-pubertal rams, with morphological changes persisting into adulthood. Environmental Toxicology and Pharmacology, 100, 104152. (doi: 10.1016/j.etap.2023.104152) (PMID:37209889)

Abstract

Environmental chemical (EC) exposure may be impacting male reproductive health. The translationally relevant biosolids treated pasture (BTP) sheep model was used to investigate gestational low-level EC mixture exposure on the testes of F1 male offspring. Adult rams from ewes exposed to BTP 1 month before and throughout pregnancy had more seminiferous tubules with degeneration and depletion of elongating spermatids, indicating possible “recovery” from previously reported testicular dysgenesis syndrome-like phenotype in neonatal and pre-pubertal BTP lambs. Expression of transcription factors CREB1 (neonatal) and BCL11A and FOXP2 (pre-pubertal) were significantly higher in the BTP exposed testes, with no changes seen in adults. Increased CREB1, which is crucial for testes development and regulation of steroidogenic enzymes, could be an adaptive response to gestational EC exposure to facilitate the phenotypic recovery. Overall, this demonstrates that testicular effects from gestational exposure to low-level mixtures of ECs can last into adulthood, potentially impacting fertility and fecundity.

• 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
• Authors: Elcombe, C. S., Monteiro, A., Ghasemzadeh-Hasankolaei, M., Padmanabhan, V., Lea, R., Sinclair, K. D., 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: 18 May 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Environmental Toxicology and Pharmacology 100: 104152
• 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