PM2.5 exposure impairs sperm quality through testicular damage dependent on NALP3 inflammasome and miR-183/96/182 cluster targeting FOXO1 in mouse

Lixiao Zhou; Xuan Su; Binghua Li; Chen Chu; Hongyue Sun; Ning Zhang; Bin Han; Chen Li; Bingjie Zou; Yujie Niu; Rong Zhang

doi:10.1016/j.ecoenv.2018.10.108

PM2.5 exposure impairs sperm quality through testicular damage dependent on NALP3 inflammasome and miR-183/96/182 cluster targeting FOXO1 in mouse

Ecotoxicol Environ Saf. 2019 Mar:169:551-563. doi: 10.1016/j.ecoenv.2018.10.108. Epub 2018 Nov 24.

Authors

Lixiao Zhou¹, Xuan Su¹, Binghua Li², Chen Chu¹, Hongyue Sun¹, Ning Zhang¹, Bin Han¹, Chen Li¹, Bingjie Zou¹, Yujie Niu³, Rong Zhang⁴

Affiliations

¹ Department of Toxicology, Hebei Medical University, Shijiazhuang, China.
² Department of Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang, China.
³ Department of Toxicology, Hebei Medical University, Shijiazhuang, China; Department of Hebei Key Laboratory of Environment and Human Health, Shijiazhuang, China.
⁴ Department of Toxicology, Hebei Medical University, Shijiazhuang, China; Department of Hebei Key Laboratory of Environment and Human Health, Shijiazhuang, China. Electronic address: rongzhang@hebmu.edu.cn.

PMID: 30476817
DOI: 10.1016/j.ecoenv.2018.10.108

Abstract

Exposure to ambient fine particular matter (PM2.5) has been clearly associated with male reproductive disorders. However, very limited toxicological studies were carried out to investigate the potential mechanisms underlying the PM2.5-induced sperm quality decline. In the present study, we established a real time whole-body PM2.5 exposure mouse model to investigate the effects of PM2.5 on sperm quality and its potential mechanisms. Sixty male C57BL/6 mice were randomly subjected to three groups: filtered air group, unfiltered air group and concentrated air group. Half of the mice from each group were sacrificed for study when the exposure duration accumulated to 8 weeks and the rest of the mice were sacrificed when exposed for 16 weeks. Our results suggested that PM2.5 exposure could induce significant increases in circulating white blood cells and inflammation in lungs. PM2.5 exposure induced apparently DNA damages and histopathologic changes in testes. There were significantly decreased sperm densities of mice, which were paralleled with the down-regulated testosterone levels in testes tissue of mice after exposure to PM2.5 for 16 weeks. The numbers of motile sperms were decreased and sperms with abnormal morphology were increased after PM2.5 exposure in a time-depended and dose-depended manner. PM2.5 exposure significantly increased the expression of the major components of the NACHT, LRR and PYD domains-containing protein3 (NALP3) inflammasome, accompanied by the increased expression of miR-183/96/182 targeting FOXO1 in testes. The present data demonstrated that sperm quality decline induced by PM2.5 could be partly explained by the inflammatory reaction in testes which might be a consequence of systemic inflammation. The molecular mechanism was depended on the activation of NALP3 inflammasome accompanied by miR-183/96/182 targeting FOXO1 in testes.

Keywords: Ambient fine particular matter (PM2.5); FOXO1; Male reproductive system; NALP3 inflammasome; Sperm quality.

MeSH terms

Air Pollutants / analysis
Air Pollutants / toxicity*
Animals
Forkhead Box Protein O1 / metabolism*
Inflammasomes / metabolism*
Male
Mice
Mice, Inbred C57BL
MicroRNAs / metabolism*
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
Particle Size
Particulate Matter / analysis
Particulate Matter / toxicity*
Random Allocation
Spermatozoa / drug effects*
Spermatozoa / metabolism
Spermatozoa / pathology
Testis / drug effects*
Testis / metabolism
Testis / pathology

Substances

Air Pollutants
Forkhead Box Protein O1
Foxo1 protein, mouse
Inflammasomes
MicroRNAs
NLR Family, Pyrin Domain-Containing 3 Protein
Nlrp3 protein, mouse
Particulate Matter