Identification of abnormal protein expressions associated with mouse spermatogenesis induced by cyclophosphamide.

ABSTRACT

Cyclophosphamide (CP) is a clinical anticancer drug that can cause male reproductive abnormalities, but the underlying mechanisms for this remain unknown. The present study aimed to explore the potential toxicity induced by CP in spermatogenesis events of germ cell proliferation, meiosis, and blood-testis barrier integrity at the molecular level. CP-treated mice showed significantly reduced serum testosterone levels, sperm motility and concentration. The results of immunohistochemistry and Western blot showed that CP reduced the proliferation of germ cells (PCNA, PLZF) and increased germ cell apoptosis (Bax and TUNEL-positive cells) in CP-treated mice testes. The expression of meiotic related proteins (SYCP3, REC8, MLH1) decreased significantly in the fourth week after administration, and the expression of blood-testis barrier related proteins (ß-catenin, ZO-1) and sperm quality-associated proteins (PGK2, HSPA4) decreased significantly in the first week after administration. CP leads to the apoptosis of male germ cells, inhibits the proliferation of germ cells, and affects meiosis and the blood-testis barrier, resulting in the decline of sperm quality. This study provides information to further the study of molecular mechanism and protective strategy of CP influence.