Low dose chlorothalonil impairs mouse spermatogenesis through the intertwining of Estrogen Receptor Pathways with histone and DNA methylation

Abstract

Recently, environment contaminants including pesticides, fungicides, mycotoxin and others chemicals have been suggested to be responsible for the decline in the human spermatozoa quality especially motility and the increase in infertility rate. Chlorothalonil is used widely for protection of vegetables and crops because it is a broad spectrum fungicide. It has been reported that chronic occupational exposure to fungicides was associated with poor spermatozoa morphology in young men. The pubertal period is very important for the male reproductive system development due to spermatogonial cell proliferation, the expansion of meiotic and haploid germ cells. Although some investigations have studied the male reproductive toxicity of chlorothalonil, almost no studies focused on spermatogenesis. The aim of our current investigation was to explore the impacts of chlorothalonil on spermatogenesis and the underlying mechanisms. It demonstrates: i) chlorothalonil decreased boar spermatozoa motility in vitro and increased the cell apoptosis; ii) chlorothalonil inhibited mouse spermatogenesis in vivo; iii) chlorothalonil disturbed spermatogenesis through the disruption of estrogen receptor signalling; iv) chlorothalonil disrupted histone methylation and DNA methylation which might be through estrogen signalling pathways. Due to the over use or incorrect use, chlorothalonil might cause serious problems to human health, especially spermatogenesis. Therefore we strongly recommend that greater attention should be paid to this fungicide to minimise its impact on human health especially spermatogenesis.