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核酸内切酶 G 在小鼠精子发生过程中对于精子线粒体 DNA 的消除是可有可无的。

Endonuclease G is dispensable for sperm mitochondrial DNA elimination during spermatogenesis in mice.

机构信息

Guangdong Second Provincial General Hospital, Postdoctoral Research Station of Basic Medicine, School of Medicine, Jinan University, Guangzhou, 510317, Guangdong, China.

Guangzhou Key Laboratory of Metabolic Diseases and Reproductive Health, Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, Guangdong, China.

出版信息

Biol Open. 2024 Jul 15;13(10). doi: 10.1242/bio.061730. Epub 2024 Oct 7.

DOI:10.1242/bio.061730
PMID:39373150
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11554256/
Abstract

Maternal inheritance of mitochondrial DNA (mtDNA) is a widespread phenomenon in eukaryotes. Our earlier research indicated that sperm mtDNA is removed prior to fertilization in mice, and Endonuclease G (ENDOG) orchestrates the degradation of sperm mitochondria in Caenorhabditis elegans. However, the mechanisms underlying sperm mtDNA disposal in mammals remain poorly understood. To investigate the potential role of ENDOG in sperm mtDNA elimination, we created Endog knockout (Endog-/-) mice. Our findings revealed that Endog-/- mice maintained normal spermatogenesis and fertility. Most strikingly, we detected no substantial discrepancy in sperm mtDNA copy number between Endog-/- and control mice. Furthermore, we noted that sperm mtDNA copy numbers were unchanged in both less motile and motile sperm isolated by Percoll gradient centrifugation from Endog-/- and control mice. Taken together, our results indicate that ENDOG is not essential for spermatogenesis or the elimination of sperm mtDNA in mice.

摘要

线粒体 DNA（mtDNA）的母系遗传是真核生物中广泛存在的现象。我们之前的研究表明，在小鼠中，精子 mtDNA 在受精前被清除，而 Endonuclease G（ENDOG）在秀丽隐杆线虫中协调精子线粒体的降解。然而，哺乳动物中精子 mtDNA 处理的机制仍知之甚少。为了研究 ENDOG 在精子 mtDNA 消除中的潜在作用，我们创建了 Endog 敲除（Endog-/-）小鼠。我们的研究结果表明，Endog-/- 小鼠维持正常的精子发生和生育能力。最引人注目的是，我们在 Endog-/- 和对照小鼠的精子 mtDNA 拷贝数之间没有发现实质性差异。此外，我们注意到，从 Endog-/- 和对照小鼠的 Percoll 梯度离心分离的运动能力较低和运动能力较强的精子中，精子 mtDNA 拷贝数没有变化。综上所述，我们的结果表明，ENDOG 对于小鼠的精子发生或精子 mtDNA 的消除不是必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/11554256/2dd1eb0b9440/biolopen-13-061730-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/11554256/be2f7e6fa34c/biolopen-13-061730-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/11554256/a68a3f115b6c/biolopen-13-061730-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/11554256/2dd1eb0b9440/biolopen-13-061730-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/11554256/be2f7e6fa34c/biolopen-13-061730-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/11554256/a68a3f115b6c/biolopen-13-061730-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58e4/11554256/2dd1eb0b9440/biolopen-13-061730-g3.jpg

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本文引用的文献

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Molecular basis for maternal inheritance of human mitochondrial DNA.人类线粒体 DNA 母系遗传的分子基础。
Nat Genet. 2023 Oct;55(10):1632-1639. doi: 10.1038/s41588-023-01505-9. Epub 2023 Sep 18.
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Loss-of-function mutations in CFAP57 cause multiple morphological abnormalities of the flagella in humans and mice.CFAP57 基因功能丧失性突变导致人类和小鼠的鞭毛多种形态异常。
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Biallelic HFM1 variants cause non-obstructive azoospermia with meiotic arrest in humans by impairing crossover formation to varying degrees.
双等位基因 HFM1 变异导致人类非梗阻性无精子症，减数分裂阻滞，不同程度地损害了交叉形成。
Hum Reprod. 2022 Jun 30;37(7):1664-1677. doi: 10.1093/humrep/deac092.
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Assessment of the Role of Nuclear ENDOG Gene and mtDNA Variations on Paternal Mitochondrial Elimination (PME) in Infertile Men: An Experimental Study.评估核内 ENDOG 基因和 mtDNA 变异对男性不育患者父系线粒体清除（PME）的作用：一项实验研究。
Reprod Sci. 2022 Aug;29(8):2208-2222. doi: 10.1007/s43032-022-00953-8. Epub 2022 Apr 27.
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Mitochondrial DNA content reduction in the most fertile spermatozoa is accompanied by increased mitochondrial DNA rearrangement.最优质的精子中存在线粒体 DNA 含量减少，同时伴有线粒体 DNA 重排增加。
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Endonuclease G promotes autophagy by suppressing mTOR signaling and activating the DNA damage response.核酸内切酶 G 通过抑制 mTOR 信号通路和激活 DNA 损伤反应促进自噬。
Nat Commun. 2021 Jan 20;12(1):476. doi: 10.1038/s41467-020-20780-2.
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Molecular insights into the divergence and diversity of post-testicular maturation strategies.对精子后熟化策略的分歧和多样性的分子洞察。
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Mitochondrial DNA: Distribution, Mutations, and Elimination.线粒体 DNA：分布、突变与消除。
Cells. 2019 Apr 25;8(4):379. doi: 10.3390/cells8040379.
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