PRSS50 介导的 MKP3/ERK 信号抑制对减数分裂进程和精子质量至关重要。

IF 4 1区 生物学 Q1 ZOOLOGY Zoological Research Pub Date : 2024-09-18 DOI:10.24272/j.issn.2095-8137.2023.388
Chun-Xue Niu, Jia-Wei Li, Xiao-Li Li, Lin-Lin Zhang, Yan Lang, Zhen-Bo Song, Chun-Lei Yu, Xiao-Guang Yang, Hai-Feng Zhao, Jia-Ling Sun, Li-Hua Zheng, Xue Wang, Ying Sun, Xiao-Hong Han, Guan-Nan Wang, Yong-Li Bao
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引用次数: 0

摘要

丝氨酸蛋白酶 50(PRSS50/TSP50)在精母细胞中高度表达。我们的研究调查了它在睾丸发育和精子生成中的作用。最初,我们观察到 PRSS50 基因敲除会影响精母细胞的 DNA 合成。为了进一步探讨这个问题,我们产生了PRSS50基因敲除(Prss50 -/- )小鼠(麝鼠),它们表现出精子核压缩异常和雄性生育能力下降。此外,在4周龄的Prss50 -/-小鼠身上还观察到发育不良的曲细精管和性激素减少,同时伴有减数分裂进展缺陷和生精细胞凋亡增加。机理分析表明,PRSS50缺失会导致细胞外信号调节蛋白激酶1和2(ERK1/2)磷酸化增加,以及MAP激酶磷酸酶3(MKP3)(一种特异性ERK拮抗剂)水平升高,这可能是青春期Prss50 -/-小鼠睾丸发育不良的原因。综上所述,这些研究结果表明,PRSS50在睾丸发育和精子生成过程中发挥着重要作用,而MKP3/ERK信号通路在这一过程中发挥着重要作用。
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PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality.

Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.

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来源期刊
Zoological Research
Zoological Research Medicine-General Medicine
CiteScore
7.60
自引率
10.20%
发文量
1937
审稿时长
8 weeks
期刊介绍: Established in 1980, Zoological Research (ZR) is a bimonthly publication produced by Kunming Institute of Zoology, the Chinese Academy of Sciences, and the China Zoological Society. It publishes peer-reviewed original research article/review/report/note/letter to the editor/editorial in English on Primates and Animal Models, Conservation and Utilization of Animal Resources, and Animal Diversity and Evolution.
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