Low dose carbendazim disrupts mouse spermatogenesis might Be through estrogen receptor related histone and DNA...

Pesticides, fungicides are reportedly involved in a decline in spermatozoa quality, especially motility, and a consequent increase in the rate of infertility. Fungicide carbendazim (CBZ) is widely used in agriculture and other aspects. Although CBZ is known to disrupt spermatogenesis, causing a decrease in spermatozoa concentration and motility, the mechanisms are not fully understood. We aimed to further explore the underlying mechanisms of CBZ disruption of spermatogenesis. Pubertal mice were exposed to low doses (0.1, 1 and 10 mg/kg body weight) of CBZ for 5 weeks, then many factors related to spermatogenesis have been explored. It was found that 0.1-10 mg/kg body weight of CBZ exposure decreased mouse sperm motility and concentration, diminished the important protein factors (VASA, PGK2, B-Amy and CREM) for spermatogenesis, reduced sperm protein acrosin level, disrupted very vital epigenetic factors H3K27, 5 mC and 5 hmC. Furthermore, CBZ exposure damaged estrogen receptor alpha (ERα) pathway by decreased the protein levels of ERα and its targets PI3K and AKT. In summary low doses of CBZ exposure disrupted mouse spermatogenesis through estrogen receptor signaling; and that histone methylation and DNA methylation might play vital roles in CBZ disturbance of spermatogenesis through intertwining with estrogen signaling pathways. CBZ from the contamination in environment or food chain poses a serious threat to the normal development of spermatozoa. Therefore we strongly recommend to minimise the use of CBZ since it causes the severe issues on spermatogenesis.