ABSTRACT
Spermatogenesis is a well-studied process that ultimately generates mature haploid spermatozoa from diploid spermatogonial stem cells (SSCs) through well-ordered processes of mitosis, meiosis and differentiation. It occurs in the seminiferous tubules of testes and is strictly controlled, scheduled, incessant and essential for male fertility. The SSCs are undifferentiated cells located within a specialized microenvironment called “niche,” which is precisely controlled by the somatic Sertoli cells through their paracrine secretions. Signaling molecules secreted by the Sertoli cells critically determine the SSCs’ fate by either promoting their self-renewal or initiating differentiation and entry into meiosis for the production of spermatozoa. The key to normal and continuous spermatogenesis is the dual property of the SSCs to continually self-renew and differentiate. This crucial step of spermatogenesis is critically regulated by several kinases, one of them being phosphoinositide 3-kinases (PI3K). The PI3K/Akt signaling pathway is important for regulating multiple cellular processes, including cell proliferation, survival, migration and metabolism. In the testis, the PI3K-Akt signaling pathway is activated at different steps of the spermatogenic process by key mediators such as the glial cell line-derived neurotrophic factor (GDNF), stem cell factor (SCF), c-Kit and Foxo-1. Several reports have evidenced the importance of PI3K/Akt signaling in the regulation of specific aspects of male reproductive function, such as gonadotropin release, gonadal development and spermatogenesis through multiple downstream signaling molecules exerting their effect via the common PI3K/Akt pathway. This chapter presents the role of the PI3K/Akt pathway in regulating spermatogenesis via SSCs self-renewal and proliferation or differentiation through the GDNF and SCF/c-Kit–mediated effects, respectively.
