FK506 binding protein 12.6-mediated inhibition of sperm-specific calcineurin is essential for FK506-induced male infertility by disturbing the homeostasis of calcium and mitochondria.

ABSTRACT: Impaired sperm motility is a leading cause of male infertility. Studies indicated that FK506, an immunosuppressive drug, resulted in male mouse infertility or an overall decline in the fertilization capacity of male renal transplant recipients. However, the underlying mechanism is not fully elucidated. Here, we reported that the disruption of FK506 binding protein 12.6 (FKBP12.6) significantly alleviated FK506-induced male infertility in mice by restoring sperm motility and mitochondrial functions in immature sperm. Mechanically, we identified that the FK506-FKBP12.6 complex preferentially bound to the sperm-specific calcineurin, which is composed of a catalytic subunit (PPP3CC) and a regulatory subunit (PPP3R2). We revealed that FKBP12.6 deficiency reversed FK506-induced the elevated expr

SUBMITTER: Xiao YF 

PROVIDER: S-EPMC12722626 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature