Differential impact of the kinase inhibitors ruxolitinib and ceritinib on porcine sperm in vitro

Small-molecule protein kinase inhibitors are applied for the medical treatment of several diseases (Roskoski Jr, 2016). Given the increasing use of these molecules, particularly in Cancer therapy, their influence on sperm is of great importance for a better understanding of the presumed effects on the reproductive potential and fertility of male patients. Therefore, we investigated the influence of the small-molecule kinase inhibitors ruxolitinib and ceritinib on porcine sperm in vitro. Porcine sperm were employed as a substitute for mammalian, especially human sperm, as they are available in large quantities in reproducible quality. Under all conditions, ceritinib at a molar drug/lipid ratio of 1:10 had adverse effects on sperm motility, viability and membrane integrity, while ruxolitinib at highest concentrations showed no or only weak effects on motility parameters. The massive merocyanine 540 binding in all dead and most viable ceritinib treated cells already after a short-term incubation at 38°C qualifies the disturbance of membrane lipid order as the most likely cause for the observed decrease in motility and viability. Therefore, possible damage to human sperm must be considered when administering ceritinib. The attempt to investigate a kinase-mediated influence of the inhibitors on capacitation and acrosome reaction failed because even the low concentration of the solvent DMSO interfered with this function. To test effects of small-molecule kinase inhibitor on selected properties of living cells, porcine sperm has proven to be a useful in vitro model.

Ceritinib; Drug-sperm interaction; Porcine sperm; Ruxolitinib; Small-molecule kinase inhibitors.