The protein YWHAE (14-3-3 epsilon) in spermatozoa is essential for male fertility

Background Spermatogenesis is a complex biological process highlighted by synthesis and activation of proteins that regulate meiosis and cellular differentiation occur during spermatogenesis. 14-3-3 proteins are adaptor proteins that play critical roles in kinase signaling, especially for regulation of cell cycle and apoptosis in eukaryotic cells. There are seven isoforms of the 14-3-3 family proteins encoded by seven genes (beta, epsilon, gamma, eta, theta/tau, zeta and sigma). 14-3-3 isoforms have been shown to have many interacting partners in several tissues including testis. Objective While it is known that 14-3-3 proteins are expressed in the functions of testis and spermatozoon, the role for each of the seven isoforms is not known. In this study, we investigated the roles of 14-3-3 eta and 14-3-3 epsilon isoforms in spermatogenesis. Materials and methods To study the in vivo function of 14-3-3 eta and 14-3-3 epsilon in spermatogenesis, we generated testis-specific and global knockout mice for each of 14-3-3 eta and 14-3-3 epsilon isoforms (CKO and GKO, respectively). Computer-assisted semen analysis was used to assess sperm motility, while immunohistochemical studies were conducted to check spermatogenesis. Results Although both 14-3-3 eta and 14-3-3 epsilon isoforms were present in mouse testis, only the expression of 14-3-3 epsilon, but not 14-3-3 eta, was detected in spermatozoa. Mice lacking 14-3-3 eta were normal and fertile while 14-3-3 epsilon CKO and GKO males showed infertility. Low sperm count with higher abnormal spermatozoa was seen in 14-3-3 epsilon CKO mice. The motility of 14-3-3 epsilon knockout spermatozoa was lower than that of the control. A reduction in the phosphorylation of both glycogen synthase kinase 3 and PP1 gamma 2 was also seen in spermatozoa from 14-3-3 epsilon CKO mice, suggesting a specific role of 14-3-3 epsilon in spermatogenesis, sperm motility, and fertility. Discussion and conclusion This is the first demonstration that of the seven 14-3-3 isoforms, 14-3-3 epsilon is essential for normal sperm function and male fertility.

Automated summary

Spermatogenesis is a complex biological process involving the synthesis and activation of proteins, with 14-3-3 proteins playing critical roles in regulating cell cycle and apoptosis. Among the seven isoforms, 14-3-3 epsilon has been identified as essential for normal sperm function and male fertility, with specific roles in spermatogenesis and sperm motility.