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

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.

Regulatory T cells play a crucial role in maintaining sperm tolerance and male fertility

“…6 D and E ). For instance, Treg-depleted EVs display reduced levels of proteins that play crucial roles in sperm motility ( 34 – 38 ) ( Rab5b , Rab11, Gpx4 , Acly , Adam7 , and Ywhae ), acrosome reaction ( 34 , 39 ) ( Rab5b , Rab11, and Vamp3 ), sperm–zona pellucida interaction ( 40 ) ( Hexb ), sperm–EV interaction ( 34 , 41 ) ( Mfge8 ), and some involved in signaling pathways known to regulate sperm function such as Hedgehog and Notch ( 42 – 44 ), Rho ( 45 – 47 ), Wnt ( 48 ), and MAPK ( 49 ) ( Fig. 6 D and E ).…”

Comparison of urinary proteome in the first two days after mating in male rats

“…The 14-3-3 protein plays a key regulatory role in both mitosis and meiosis. In mice, 14-3-3 protein epsilon is essential for normal sperm function and male fertility 39 . Mature spermatids need to be released from their attached sertoli cells.…”

Binding Partners of 14-3-3 (YWHA) Protein Isoforms among Mammalian Species, Tissues, and Developmental Stages

“…Protein 14-3-3 zeta binds to the protein phosphatase, PP1g2 in bovine epididymal spermatozoa [48]. Recently, it was suggested that 14-3-3 epsilon alone may be required for normal sperm function [49,50].…”