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epg5 敲除导致自噬相关疾病斑马鱼模型生殖力受损和求爱行为异常。

epg5 knockout leads to the impairment of reproductive success and courtship behaviour in a zebrafish model of autophagy-related diseases.

机构信息

Department of Biology, University of Padova, Padova, Italy.

Department of Biology, University of Padova, Padova, Italy; Department of Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn-Fano Marine Centre, Fano, Italy.

出版信息

Biomed J. 2022 Apr;45(2):377-386. doi: 10.1016/j.bj.2021.04.002. Epub 2021 Apr 20.

DOI:10.1016/j.bj.2021.04.002
PMID:35562284
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9250093/
Abstract

BACKGROUND

Dysregulation of the autophagic flux is linked to a wide array of human diseases, and recent findings highlighted the central role of autophagy in reproduction, as well as an association between impairment of autophagy and behavioural disorders. Here we deepened on the possible multilevel link between impairment of the autophagic processes and reproduction at both the physiological and the behavioural level in a zebrafish mutant model.

METHODS

Using a KO epg5 zebrafish line we analysed male breeding success, fertility rate, offspring survival, ejaculate quality, sperm and testes morphology, and courtship behaviour. To this aim physiological, histological, ultrastructural and behavioural analyses on epg5 and mutant epg5 males coupled to WT females were applied.

RESULTS

We observed an impairment of male reproductive performance in mutant epg5 males that showed a lower breeding success with a reduced mean number of eggs spawned by their WT female partners. The spermatogenesis and the ability to produce fertilising ejaculates were not drastically impaired in our mutant males, whereas we observed a reduction of their courtship behaviour that might contribute to explain their lower overall reproductive success.

CONCLUSION

Collectively our findings corroborate the hypothesis of a multilevel link between the autophagic process and reproduction. Moreover, by giving a first glimpse on behavioural disorders associated to epg5 KO in model zebrafish, our results open the way to more extensive behavioural analyses, also beyond the reproductive events, that might serve as new tools for the molecular screening of autophagy-related multisystemic and neurodegenerative diseases.

摘要

背景

自噬通量的失调与广泛的人类疾病有关,最近的研究结果强调了自噬在生殖中的核心作用,以及自噬功能障碍与行为障碍之间的关联。在这里,我们在斑马鱼突变模型中深入研究了自噬过程受损与生理和行为水平生殖之间的可能多层次联系。

方法

我们使用 KO epg5 斑马鱼系分析了雄性繁殖成功率、生育率、后代存活率、精液质量、精子和睾丸形态以及求爱行为。为此,我们对 epg5 和突变型 epg5 雄性与 WT 雌性进行了生理、组织学、超微结构和行为分析。

结果

我们观察到突变型 epg5 雄性的雄性生殖性能受损,其与 WT 雌性伴侣产卵的平均数量减少,繁殖成功率降低。我们的突变型雄性的精子发生和产生可受精精液的能力并没有受到严重损害,而我们观察到它们的求爱行为减少,这可能有助于解释它们整体繁殖成功率较低的原因。

结论

总的来说,我们的研究结果证实了自噬过程与生殖之间存在多层次联系的假设。此外,通过在模式斑马鱼中首次揭示与 epg5 KO 相关的行为障碍,我们的结果为更广泛的行为分析开辟了道路,这些分析也超越了生殖事件,可作为与自噬相关的多系统和神经退行性疾病的分子筛选的新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/84154ad51fdf/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/54149e2bbfc1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/0821836467ad/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/25bda57efdab/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/7f7d5f77dea7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/069f4eafb6f1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/84154ad51fdf/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/54149e2bbfc1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/0821836467ad/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/25bda57efdab/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/7f7d5f77dea7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/069f4eafb6f1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a76d/9250093/84154ad51fdf/gr6.jpg

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Low-level expression of EPG5 leads to an attenuated Vici syndrome phenotype.EPG5的低水平表达导致维西综合征表型减弱。
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