Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 18;45(5):1037-1047.
doi: 10.24272/j.issn.2095-8137.2023.388.

PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality

Chun-Xue Niu  1 , Jia-Wei Li  1 , Xiao-Li Li  2 , Lin-Lin Zhang  1 , Yan Lang  2 , Zhen-Bo Song  3 , Chun-Lei Yu  2 , Xiao-Guang Yang  2 , Hai-Feng Zhao  4 , Jia-Ling Sun  4 , Li-Hua Zheng  2 , Xue Wang  4 , Ying Sun  2 , Xiao-Hong Han  4 , Guan-Nan Wang  2 , Yong-Li Bao  5
Affiliations

PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality

Chun-Xue Niu et al. Zool Res. .

Abstract
in English, Chinese

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.

已有研究发现，PRSS50 (TSP50)在精母细胞中高表达，该研究旨在探讨PRSS50、在睾丸发育和精子发生中的作用。我们首先发现PRSS50的敲低会阻碍精母细胞的增殖。然后我们生成了Prss50敲除小鼠，发现它精子头部浓缩不实，雄性小鼠生育能力降低。此外，在4周龄的Prss50敲除小鼠中观察到生精小管发育不良，性激素水平降低，并伴有减数分裂过程缺陷和生精细胞过度凋亡。机制分析表明，PRSS50缺失增加了ERK1/2的磷酸化和MKP3的水平，这可能是青春期PRSS50小鼠睾丸发育不良的原因。综上所述，我们的研究结果表明，PRSS50在睾丸发育和精子发生中起着重要作用，而MKP3/ERK信号参与了这一过程。.

Keywords: ERK; MKP3; Meiotic progression; PRSS50 (TSP50); Sperm quality.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Serine protease 50 (PRSS50) knockdown affected DNA synthesis in GC-2spd cells
Figure 2
Figure 2
PRSS50 knockout affected fertility in 8-week-old male mice
Figure 3
Figure 3
PRSS50 knockout impaired sperm production
Figure 4
Figure 4
PRSS50 knockout retarded testicular tissue development in 4-week-old mice
Figure 5
Figure 5
PRSS50 knockout impeded meiotic progression
Figure 6
Figure 6
PRSS50 knockdown disturbed MKP3/ERK signaling by binding to MKP3
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Agarwal A, Baskaran S, Parekh N, et al Male infertility. The Lancet. 2021;397(10271):319–333. doi: 10.1016/S0140-6736(20)32667-2. - DOI - PubMed
    1. Agarwal A, Mulgund A, Hamada A, et al A unique view on male infertility around the globe. Reproductive Biology and Endocrinology. 2015;13:37. doi: 10.1186/s12958-015-0032-1. - DOI - PMC - PubMed
    1. Aoki VW, Liu LH, Jones KP, et al Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability. Fertility and Sterility. 2006;86(5):1408–1415. doi: 10.1016/j.fertnstert.2006.04.024. - DOI - PubMed
    1. Camps M, Nichols A, Arkinstall S Dual specificity phosphatases: a gene family for control of MAP kinase function. The FASEB Journal. 2000;14(1):6–16. doi: 10.1096/fasebj.14.1.6. - DOI - PubMed
    1. Cao QH, Liu F, Li CZ, et al Testes-specific protease 50 (TSP50) promotes invasion and metastasis by inducing EMT in gastric cancer. BMC Cancer. 2018;18(1):94. doi: 10.1186/s12885-018-4000-y. - DOI - PMC - PubMed

Substances

LinkOut - more resources