Infertility Mitochondrial Respiratory Efﬁciency is Positively Correlated With Human Sperm Motility Alessandra Ferramosca, Sara Pinto Provenzano, Lamberto Coppola, and Vincenzo Zara OBJECTIVE To correlate sperm mitochondrial respiratory efﬁciency with variations in sperm motility and with sperm morphologic anomalies. METHODS Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen con- sumption carried out in hypotonically-treated sperm cells. A possible relationship among sperm mitochondrial respiratory efﬁciency, sperm motility, and morphologic anomalies was investigated. RESULTS Mitochondrial respiratory efﬁciency was positively correlated with sperm motility and negatively correlated with the percentage of immotile spermatozoa. Moreover, midpiece defects impaired mitochondrial functionality. CONCLUSION Our data indicate that an increase in sperm motility requires a parallel increase in mitochondrial respiratory capacity, thereby supporting the fundamental role played by mitochondrial oxidative phosphorylation in sperm motility of normozoospermic subjects. These results are of physio- pathological relevance because they suggest that disturbances of sperm mitochondrial function and of energy production could be responsible for asthenozoospermia. UROLOGY 79: 809 – 814, 2012. © 2012 Elsevier Inc. M itochondria of spermatozoa signiﬁcantly differ, structurally and functionally, from the corre- sponding organelles of somatic cells. The main reason for these differences resides in the peculiarity of spermatozoa, which are terminal cells with the precise func- tion of fertilizing the oocyte in the female genital tract. Nevertheless, sperm mitochondria, as well as the somatic ones, are the location of the oxidative phosphorylation process, which is necessary for the production of metabolic energy in the form of adenosine triphosphate (ATP). The role of these organelles in sperm motility was investigated thoroughly, 1-5 mainly because the causes of asthenozoosper- mia, a fertility-impairing pathology linked to a pronounced reduction of sperm motility, are largely unknown. However, the presence of structural and functional alterations in sperm mitochondria from asthenozoospermic subjects sug- gested an important involvement of these organelles in energy production for sperm motility. 6-14 The functionality of sperm mitochondria has been inves- tigated using different technical approaches, such as spec- trophotometric or cytoﬂuorimetric methods. 7,8,12,15-19 In these studies, a positive correlation between the mito- chondrial functionality and sperm motility or, in general, the quality of semen samples, was reproducibly found. This is predictable taking into account that not only motility but also several essential sperm functions require ATP as an energy source. However, cytosolic glycolysis, another catabolic process producing ATP, was also pro- posed to play a main role in sperm motility. As a conse- quence, many researchers became involved in a long debate on this central issue. 1-4 Recently, our group de- veloped a polarographic assay for the evaluation of sperm mitochondrial respiratory efﬁciency using demem- branated human spermatozoa. 20,21 With this experimen- tal approach, the rate of mitochondrial oxygen uptake by sperm mitochondria was measured in standardized con- ditions, comparable with those generally used in the case of somatic mitochondria. The aim of this study was to correlate sperm mitochon- drial respiration, evaluated by the polarographic assay of oxygen consumption, with variations in sperm motility. In parallel, we also investigated a possible relationship between sperm mitochondrial respiratory efﬁciency and the percentage of sperm morphologic anomalies. MATERIAL AND METHODS Patients We studied 120 semen samples from the same number of patients, between 24 and 52 years of age. The ejaculates of men medically or surgically treated in the prior 3 months were From the Department of Environmental and Biological Sciences and Technologies, University of Salento, Lecce, Italy; and Biological Medical Center “Tecnomed”, Nardò (Lecce), Italy. Reprint requests: Dr. Vincenzo Zara, Department of Environmental and Biological Sciences and Technologies, University of Salento, Lecce, Italy. E-mail: vincenzo. zara@unisalento.it Submitted: October 6, 2011, accepted (with revisions): December 28, 2011 © 2012 Elsevier Inc. 0090-4295/12/$36.00 809 All Rights Reserved doi:10.1016/j.urology.2011.12.042