A non-hormonal reversible contraceptive targeting GSK3α, a protein kinase, essential for epididymal sperm maturation.

ABSTRACT:

Background and objectives

Epididymal transit renders key competence to mammalian spermatozoa for fertilizing eggs. Generally, the two paralogs of glycogen synthase kinase 3, GSK3α and GSK3β, functionally overlap except in testis and sperm. We showed that GSK3α is essential for epididymal sperm maturation and fertilization. Male infertility is the only phenotype of mice with a global or testis-specific knockout (KO) of Gsk3α. Their sperm maturation is impaired, and sperm cannot fertilize eggs in vitro and in vivo. This suggests that GSK3α is a "male fertility kinase" in mammals and that GSK3α-selective inhibitor is a potential male contraceptive.

Materials and methods

A set of eight heterozygous Gsk3α(±) male mice received daily intraperitoneal injections of BRD0705, an isofo

SUBMITTER: Kabi M 

PROVIDER: S-EPMC12569727 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature