The mechanisms in the altered ontogenetic development and lung-related pathology in microcystin-leucine arginine (MC-LR)-paternal-exposed offspring mice

Xiannan Meng, Ling Zhang, Jiwei Hou, Tan Ma, Chun Pan, Yuan Zhou, Ruitong Han, Yuanzhen Ding, Haoran Peng, Zou Xiang, Dongmei Li, Xiaodong Han

Research output: Journal article publicationJournal articleAcademic researchpeer-review

3 Citations (Scopus)

Abstract

A father's lifetime experience is a major risk factor for a range of diseases in an individual, and the consequences of the exposure can also be transmitted to his offspring. Our previous work has demonstrated that damage to testicular structures and decline in sperm quality in male mice can be caused by microcystin-leucine arginine (MC-LR), but the overall effects of the scope and extent of paternal exposure on health and disease in the offspring remain underexplored. Here, we report that MC-LR-paternal-exposed offspring mice showed reduced litter size and body weight accompanied by increased abnormalities in the lung. Analyses of the small noncoding RNAs (sncRNAs) in the sperm from MC-LR-exposed males demonstrated the downregulation of a wide range of piRNAs enriched for those target genes involved in the regulation of the embryo implantation pathways. Gene and protein expression analyses, as well as biochemical and functional studies, revealed suppressed expression of Hsp90α in testicular tissues from MC-LR-exposed males. Decreased Hsp90α in testicular tissues impaired the development of the offspring. In this study, we revealed that MC-LR alters the expression of Hsp90α in testicular tissues to cause changes in the expression profiles of sperm piRNAs produced by paternal mice. These changes lead to aberrant activation of the Wnt/β-catenin signaling pathway in pulmonary tissues of offspring mice, causing lung tissue damage and abnormal development. We hereby confirmed that MC-LR-induced alterations in epigenetic inheritance are capable of contributing to intergenerational developmental defects in paternal-exposed offspring mice.

Original languageEnglish
Article number139678
JournalScience of the Total Environment
Volume736
Early online date25 May 2020
DOIs
Publication statusPublished - 20 Sep 2020

Keywords

  • Intergenerational toxicity
  • Microcystin-LR
  • Offspring
  • Pulmonary tissue
  • Sperm piRNA
  • Water contamination

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution

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