Treatment with Hippo/YAP pathway modulators partially improves testicular and sperm phenotypes following cisplatin stimulation.

BACKGROUND

Treatment with chemotherapeutic agents often causes side effects in male reproductive organs, which may lead to infertility. Identification of molecular targets to alleviate this effect is important to reduce the long-term effects of chemotherapeutic drugs on the reproductive capacity. In this study, we evaluated the effects of pharmacological targeting of the Hippo pathway on the male reproductive system following chemotherapeutic treatment with cisplatin.

MATERIALS AND

METHODS

This is a experimental study used 12 weeks old male Balb/c mice, divided into four groups. We observed significant reduction in the numbers of spermatocytes, spermatids, Sertoli cells, and Leydig cells in the testes following cisplatin treatment. We then used two different types of Hippo pathway modulators to treat cisplatin-induced testicular and sperm phenotypes: i) XMU-MP-1, which is a strong inhibitor of mammalian sterile 20-like kinase 1/2, and ii) TT-10, which stimulates yes-associated protein (YAP) activity. We performed the analysis using the GraphPad Prism software. If the data were regularly distributed, we would compare the means of the two groups using a parametric test called the Student's t-test. A non-parametric test (Mann-Whitney U test) was employed if the data were not regularly distributed.

RESULTS

We found that treatment with XMU-MP-1 significantly increased Leydig cell numbers. However, there was no change in sperm phenotype despite a significant improvement in sperm motility. In contrast, TT-10 treatment improved sperm concentration and morphology, and increased Leydig cell number.

CONCLUSIONS

Our data suggest that pharmacological modulation of the Hippo/YAP pathway may improve sperm and testicular phenotypes in mice following treatment with chemotherapeutic agents, such as cisplatin.