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通过激活ERK信号通路促进精原干细胞增殖。

Promotes the Proliferation of Spermatogonial Stem Cells by Activating ERK Signaling.

作者信息

Zhang Mengfei, Li Na, Liu Wenqing, Du Xiaomin, Wei Yudong, Yang Donghui, Zhou Zhe, Ma Fanglin, Peng Sha, Zhang Shiqiang, He Xin, Bai Chunling, Li Guangpeng, Hua Jinlian

机构信息

College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.

State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China.

出版信息

Stem Cells Int. 2021 Jan 29;2021:6668658. doi: 10.1155/2021/6668658. eCollection 2021.

DOI:10.1155/2021/6668658
PMID:33603791
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7869416/
Abstract

The future fertility of males with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Spermatogonial stem cell transplantation is believed to be a way to restore fertility in men. However, the survival efficiency of transplanted cells is still low. Eukaryotic translation initiation factor 2 subunit 3 and structural gene Y-linked () located on the Y chromosome of male animals is a coding gene of eIF2 which mainly functions in translation initiation. Recently, the emerging role of in spermatogenesis has been emphasized in several studies. However, the underlying mechanism is still unclear. In addition, how functions in large animals remains largely unknown. In this study, we obtained the CDS sequence of the gene from the testis of dairy goats and found that this gene was highly expressed in the testis and was evolutionarily conserved among different species. Interestingly, overexpression of promoted the proliferation of spermatogonial stem cells of dairy goats by activating the ERK signaling pathway. In animal experiments, overexpressing promoted transplanted goat spermatogonial stem cells and produced more colonies after microinjection into the seminiferous tubules of infertile mice. In conclusion, our study highlights an undiscovered role of in dairy goat reproduction. This finding may provide an important basis for future works regarding male spermatogenic cell restoration and represent a major advance toward surrogate sires becoming a tool for disseminating and regenerating germplasm in all mammals.

摘要

癌症男性患者的未来生育能力可能会因化疗和/或放疗而受到不可逆转的损害。精原干细胞移植被认为是恢复男性生育能力的一种方法。然而,移植细胞的存活效率仍然很低。真核翻译起始因子2亚基3和位于雄性动物Y染色体上的结构基因Y连锁()是eIF2的一个编码基因,主要在翻译起始中发挥作用。最近,几项研究强调了其在精子发生中的新作用。然而,其潜在机制仍不清楚。此外,它在大型动物中的功能在很大程度上仍然未知。在本研究中,我们从奶山羊睾丸中获得了该基因的CDS序列,发现该基因在睾丸中高度表达,并且在不同物种间具有进化保守性。有趣的是,该基因的过表达通过激活ERK信号通路促进了奶山羊精原干细胞的增殖。在动物实验中,过表达该基因促进了移植的山羊精原干细胞的生长,并在显微注射到不育小鼠的生精小管后产生了更多的集落。总之,我们的研究突出了该基因在奶山羊繁殖中未被发现的作用。这一发现可能为未来关于雄性生精细胞恢复的研究提供重要依据,并代表着朝着将代孕父本作为所有哺乳动物种质传播和再生工具迈出的重要一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/f2ba3ae9040a/SCI2021-6668658.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/1a63f38f2901/SCI2021-6668658.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/6096cfb8dac9/SCI2021-6668658.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/f2ba3ae9040a/SCI2021-6668658.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/1a63f38f2901/SCI2021-6668658.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/62c5c097f57d/SCI2021-6668658.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/4b656b38c280/SCI2021-6668658.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/32f3505d1542/SCI2021-6668658.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/c7ae23b4f58a/SCI2021-6668658.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/6096cfb8dac9/SCI2021-6668658.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc68/7869416/f2ba3ae9040a/SCI2021-6668658.007.jpg

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Autologous transplantation of spermatogonial stem cells restores fertility in congenitally infertile mice.自体移植精原干细胞可恢复先天性不育小鼠的生育能力。
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Exposure to Chemotherapy During Childhood or Adulthood and Consequences on Spermatogenesis and Male Fertility.儿童期或成年期接触化疗药物对精子发生和男性生育力的影响。
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YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells.
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