Decreased Spermatogenesis, Fertility, and Altered Slc2A Expression in Akt1-/- and Akt2-/- Testes and Sperm

Akt is serine/threonine protein kinase associated with various cellular processes and 3 different isoforms exist. This work describes the reproductive phenotype of Akt1-/- and Akt2-/- in male mice. The seminiferous tubule diameter in Akt1-/- testes was less than wild-type or Akt2-/- testes. The expression of phospho-phosphatase and tensin homologue deleted on chromosome 10 (p-PTEN) and phospho-glycogen synthase kinase 3 beta (GSK-3 beta) was elevated in Akt1-/- testes. Alterations in expression and localization to the plasma membrane of several facilitative glucose transporters (Slc2a8, 9a and 9b) were detected in these knockout compared to wild-type mice. Apoptotic sperm were more prevalent in both null mice compared to wild-type mice, whereas sperm concentration and motility were significantly lower in the null sperm. Finally, Akt2-/- sperm had a markedly decreased fertilization rate by in vitro fertilization (IVF) and resulting embryos displayed increased fragmentation and poor growth. These results suggest that altered SLC2A expression and increased PTEN and GSK3b activity may be responsible for the decreased spermatogenesis, sperm maturation, and fertilization in the Akt1-/- and Akt2-/- male mice.