Objective : The aim of this systematic review is to provide the first comprehensive overview of the current knowledge regarding the role of the alpha-Klotho protein in male and female fertility, focusing on the testicle, spermatozoa, ovary, and oocyte.

Results : The Klotho protein levels decrease with age. This decline influences male fertility by impacting spermatogenesis, sperm maturation, androgen production, and local homeostasis. In women, KL influences ovulatory function by inhibiting hypothalamic gonadotropin-releasing hormone secretion, regulating growth hormone secretion and oocyte quality, and controlling granulosa cells and follicular apoptosis. Overall, animal and human studies indicate that Klotho is an important factor in fertility, contributing to sperm quality and oocyte maturation and development. Additionally, the antioxidant properties of KL may help preserve the integrity of sperm cells and could serve as an effective antioxidant for the cryopreservation of ovarian tissue.

Conclusion : Further research is warranted to fully understand the mechanisms underlying the role of KL protein in human fertility, both as a potential biomarker and as a therapeutic target for infertility treatments and fertility preservation strategies. Advances in functional genetic variations studies will clarify the pathways linking genotype to phenotype in reproductive health