**5. Conclusions**

In conclusion, we reported the unexpected long-term e ffects of t-BHP treatment in the male rat reproductive system that impairs sperm quality after one complete cycle of spermatogenesis. The epididymis, in contrast to the testis, was primarily a ffected by the treatment displaying markers of oxidative stress such as high levels of 4-HNE up to 9 weeks after the end of the treatment. An antioxidant response by the upregulation of PRDX6 and possibly PRDX1 and catalase attempt to correct the oxidative stress in the epididymis results in the decrease of lipid peroxidation at 9 weeks in cauda epididymis, but it appears not to be su fficient to repair the oxidative damage observed in spermatozoa. Further studies will be needed to elucidate the molecular mechanism that generates long-term oxidative stress that impairs sperm quality and fertility. These studies are relevant since many conditions such as diseases (i.e., cancer, diabetes), drugs and even lifestyles (i.e., smoking) generate chronic oxidative stress that impacts male fertility.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2076-3921/9/2/170/s1, Table S1: Body and reproductive organs weight and sperm production.

**Author Contributions:** C.O. designed the experiments; P.Y.W. and E.S. performed the experiments; P.Y.W., E.S. and C.O. analyzed the results. P.Y.W. wrote the original draft; P.Y.W., E.S. and C.O. revised and edited the final version of the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the Canadian Institutes of Health Research (CIHR), operating gran<sup>t</sup> # MOP133661 to CO.

**Acknowledgments:** We thank Yannan Liu and Jeremie Desrosiers for their technical assistance.

**Conflicts of Interest:** The authors declare no conflict of interest.
