**6. Conclusions**

Overall, this review highlights mechanisms contributing to an OS-induced decline in sperm motility associated with conditions such as asthenozoospermia. A clear consensus to emerge from the reviewed literature is that the presence of OS in the male reproductive tract is strongly and positively correlated with reduced sperm motility. This state of OS can be evoked not only by intrinsic factors but also by a diversity of environmental agents commonly encountered during modern life. Thus, the

challenges presented to the male reproductive tract in terms of mounting an effective and prolonged defense against ROS can result in an attenuation of antioxidant capacity and a concomitant acceleration of OS-induced sperm damage. One particular pathway that appears to contribute to much of the OS response is that of LPO, which is responsible for the generation of highly reactive aldehyde species. These electrophiles are able to adversely impact sperm motility via the adduction and dysregulation of proteins involved in sperm bioenergetic pathways as well as the structural and signaling components of the motility apparatus. Given that these lesions go hand in hand with oxidative DNA damage, it is possible that they may serve a physiological role in terms of reducing the likelihood of such sperm from participating in fertilization and thus transmitting an altered paternal genome to the next generation. This possibility emphasizes the need for the development of novel therapeutic interventions to address the burden of OS-mediated dysfunction in the male germline.

**Author Contributions:** Conceptualization, K.N.-B. and B.N.; writing—original draft preparation, K.N.-B.; writing—review and editing, B.N. All authors have read and agreed to the published version of the manuscript.

**Funding:** Support was provided by a National Health and Medical Research Council of Australia (NHMRC) Project Grant (APP1163319) awarded to BN. BN is the recipient of a NHMRC Senior Research Fellowship.

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