Combined exposure to noise and CO induces adverse male reproductive effects in rats

To explore the male reproductive toxicity in rats caused by single or combined exposure to noise and carbon monoxide（CO）in closed cabin, and evaluate the joint effects and associated signal pathways.

Fifty male SD rats were randomly divided into blank control group, restraint group（negative control group）, noise exposure group, CO exposure group and combined group（n=10）. According to the poisoning procedure, the rats were fixed in the oral and nasal toxic cup and placed in the chamber and they were poisoned for 2 h per day for 30 consecutive days. The sperm quality, including sperm motility and sperm density, was analyzed after exposure, and the apoptosis of testicular cells was determined by TUNEL staining. The testicular tissues were harvested for circRNA sequencing, and the sequencing data were analyzed by bioinformatics enrichment.

After exposure to noise and CO, the semen density of the noise group and combine group was decreased significantly（P<0.05）. The sperm motility was obviously lower in the CO group than the negative control group（P<0.05）, and more serious decline was observed in the combined group（P<0.05）. Morphological study showed that there were a few vacuoles in the testis of rats exposed to noise or CO and much more vacuoles in the testis of rats exposed to combination. Obvious pathological damage was found in the testis of rats combined exposed to noise and CO, and the cells in the seminiferous tubules were in a disordered arrangement. The number of apoptotic cells was increased in the noise and CO group, and the number was the largest in the combined group. The results of sequencing analysis suggested that key circRNA and their regulated key molecules might be involved in the reproductive damage effects of noise and CO exposure on rat testes, including Smc4, Sycp1, Sycp3, Spag17, Mns1, Top2a and Rock1, which played important roles in meiosis, spermatogenesis, cell cycle and apoptosis pathways.

Combined exposure to noise and CO shows typical joint effect on male reproductive damages, which are associated with circRNAs regulation.