The protein YWHAE (14‐3‐3 epsilon) in spermatozoa is essential for male fertility. (5th August 2020)

• Record Type: Journal Article
• Authors: Eisa, Alaa; Dey, Souvik; Ignatious, Alex; Nofal, Wesam; Hess, Rex A.; Kurokawa, Manabu; Kline, Douglas; Vijayaraghavan, Srinivasan
• Is Part Of: Andrology. Volume 9:Number 1(2021)
• Page Start: 312
• Page End: 328
• Publication Date: 2020-08-05
• Subjects: 14‐3‐3 -- infertility -- sperm motility -- spermatogenesis -- YWHA; Andrology -- Periodicals; 616.65
• DOI: 10.1111/andr.12865
• Languages: English
• ISSNs: 2047-2919

Abstract

Abstract: 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 (β, ε, γ, η, θ/τ, ζ and σ). 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 14‐3‐3η and 14‐3‐3ε isoforms in spermatogenesis. Materials and methods: To study the in vivo function of 14‐3‐3η and 14‐3‐3ε in spermatogenesis, we generated testis‐specific and global knockout mice for each of 14‐3‐3η and 14‐3‐3ε 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 14‐3‐3η and 14‐3‐3ε isoforms were present in mouse testis, only the expression of 14‐3‐3ε, but not 14‐3‐3η, was detected in spermatozoa. Mice lacking 14‐3‐3η were normal and fertile while 14‐3‐3ε CKO and GKO males showed infertility. Low sperm count with higher abnormal spermatozoa was seen in 14‐3‐3ε CKO mice. The motility of 14‐3‐3ε knockout spermatozoa was lower than that of the control. A reduction in the phosphorylation of both glycogen synthase kinase 3 and PP1γ2 was also seen in spermatozoa from 14‐3‐3ε CKO mice, suggesting a specific role of 14‐3‐3ε in spermatogenesis, sperm motility, and fertility. Discussion and conclusion: This is the first demonstration that of the seven 14‐3‐3 isoforms, 14‐3‐3ε is essential for normal sperm function and male fertility.