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, Chris S.; Monteiro, Ana; Ghasemzadeh-Hasankolaei, Mohammad; Padmanabhan, Vasantha; Lea, Richard; Sinclair, Kevin D.; Evans, Neil P.; Bellingham, Michelle

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.

Citation

Elcombe, C. S., Monteiro, A., Ghasemzadeh-Hasankolaei, M., Padmanabhan, V., Lea, R., Sinclair, K. D., …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, Article 104152. https://doi.org/10.1016/j.etap.2023.104152

• Journal Article Type: Article
• Acceptance Date: May 17, 2023
• Online Publication Date: May 18, 2023
• Publication Date: Jun 1, 2023
• Deposit Date: Aug 16, 2023
• Publicly Available Date: Aug 18, 2023
• Journal: Environmental Toxicology and Pharmacology
• Print ISSN: 1382-6689
• Electronic ISSN: 1872-7077
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 100
• Article Number: 104152
• DOI: https://doi.org/10.1016/j.etap.2023.104152
• Keywords: Developmental toxicity; Reproductive toxicity; Environmental chemicals; Testicular dysgenesis syndrome; CREB
• Public URL: https://nottingham-repository.worktribe.com/output/21376723
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1382668923000947?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: 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; Journal Title: Environmental Toxicology and Pharmacology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.etap.2023.104152; Content Type: article; Copyright: © 2023 The Authors. Published by Elsevier B.V.