精子中的蛋白质 YWHAE（14-3-3 epsilon）对于男性生育能力至关重要。
The protein YWHAE (14-3-3 epsilon) in spermatozoa is essential for male fertility.
机构信息
Department of Medical Laboratories Technology, College of Applied Medical Sciences, Taibah University, Madina, Saudi Arabia.
Biology Department, Kent State University, Kent, OH, USA.
出版信息
Andrology. 2021 Jan;9(1):312-328. doi: 10.1111/andr.12865. Epub 2020 Aug 5.
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.
背景
精子发生是一个复杂的生物学过程，在此过程中会合成和激活多种蛋白质，这些蛋白质在减数分裂和细胞分化中发挥重要作用。14-3-3 蛋白是衔接蛋白，在激酶信号转导中发挥关键作用，尤其是在真核细胞的细胞周期和细胞凋亡调控中。14-3-3 蛋白家族由七个基因（β、ε、γ、η、θ/τ、ζ 和 σ）编码，有七种同工型。在多种组织中，包括睾丸，已经发现 14-3-3 同工型有许多相互作用的伴侣。
目的
虽然已知 14-3-3 蛋白在睾丸和精子的功能中表达，但七种同工型中的每一种的作用尚不清楚。在这项研究中，我们研究了 14-3-3η 和 14-3-3ε 同工型在精子发生中的作用。
材料和方法
为了研究 14-3-3η 和 14-3-3ε 在精子发生中的体内功能，我们分别生成了 14-3-3η 和 14-3-3ε 同工型的睾丸特异性和全局敲除小鼠（CKO 和 GKO）。利用计算机辅助精液分析评估精子的运动能力，同时进行免疫组织化学研究以检查精子发生情况。
结果
虽然 14-3-3η 和 14-3-3ε 同工型都存在于小鼠睾丸中，但只有 14-3-3ε 同工型，而不是 14-3-3η 同工型，在精子中被检测到。缺乏 14-3-3η 的小鼠正常且具有生育能力，而 14-3-3ε CKO 和 GKO 雄性表现出不育。14-3-3ε CKO 小鼠的精子计数较低，异常精子较多。14-3-3ε 敲除精子的运动能力低于对照。还观察到 14-3-3ε CKO 小鼠精子中糖原合酶激酶 3 和 PP1γ2 的磷酸化减少，这表明 14-3-3ε 在精子发生、精子运动和生育力中具有特定作用。
讨论与结论
这是首次证明在七种 14-3-3 同工型中，14-3-3ε 对于正常精子功能和男性生育能力是必需的。
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