Sex and tissue-specificity of piRNA regulation in adult mice following perinatal lead (Pb) exposure

Bambarendage P. U. Perera; Kai Wang; Dongyue Wang; Kathleen Chen; Alisa Dewald; Swati Sriram; Jaclyn M. Goodrich; Laurie K. Svoboda; Maureen A. Sartor; Dana C. Dolinoy

doi:10.1080/15592294.2024.2426952

Epigenetics (Dec 2024)

Sex and tissue-specificity of piRNA regulation in adult mice following perinatal lead (Pb) exposure

Bambarendage P. U. Perera,
Kai Wang,
Dongyue Wang,
Kathleen Chen,
Alisa Dewald,
Swati Sriram,
Jaclyn M. Goodrich,
Laurie K. Svoboda,
Maureen A. Sartor,
Dana C. Dolinoy

Affiliations

Bambarendage P. U. Perera: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
Kai Wang: Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Palmer Commons, Ann Arbor, MI, USA
Dongyue Wang: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
Kathleen Chen: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
Alisa Dewald: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
Swati Sriram: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
Jaclyn M. Goodrich: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
Laurie K. Svoboda: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA
Maureen A. Sartor: Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Palmer Commons, Ann Arbor, MI, USA
Dana C. Dolinoy: Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA

DOI: https://doi.org/10.1080/15592294.2024.2426952
Journal volume & issue: Vol. 19, no. 1

Abstract

Read online

Lead (Pb) is a neurotoxicant with early life exposure linked to long-term health effects. Piwi-interacting RNAs (piRNAs) are small non-coding RNAs that associate with PIWIL proteins to induce DNA methylation. It remains unknown whether Pb exposure influences piRNA expression. This study evaluated how perinatal Pb exposure (32 ppm in drinking water) impacts piRNA expression in adult mice and assessed piRNA dysregulation as a potential mechanism for Pb-induced toxicity. Pb exposure effects on piRNA expression and associated gene repression in the germline (testis/ovary) and soma (liver and brain) were evaluated. Small RNA sequencing was used to determine differentially expressed piRNAs, RT-qPCR to examine piRNA target expression, and whole genome bisulfite sequencing to evaluate target DNA methylation status. Three piRNAs (mmpiR-1500602, mmpiR-0201406, and mmpiR-0200026) were significant after multiple testing correction (all downregulated in the male Pb-exposed brain in comparison to control; FDR < 0.05). Within piOxiDB, TAO Kinase 3 was identified as a downstream mRNA target for one of the three Pb-sensitive piRNA. The Pb-exposed male brain exhibited increased Taok3 expression (p < 0.05) and decreased DNA methylation (FDR < 0.01). The results demonstrate that perinatal Pb exposure stably influences longitudinal piRNA expression in a tissue- and sex-specific manner, potentially via DNA methylation-directed mechanisms.

Published in Epigenetics

ISSN: 1559-2294 (Print); 1559-2308 (Online)
Publisher: Taylor & Francis Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Genetics
Website: https://www.tandfonline.com/kepi

About the journal

Abstract

Keywords