Dissecting sperm mitochondrial G-quadruplex structures using a fluorescent probe biomarker to monitor and regulate fertilization capability

Wu, Sixian, Li, Xiaoliang, Huang, Gelin, Guo, Juncen, Zhang, Xueguang, Liao, Lu, Zhi, Weiwei, Li, Kun, Wang, Yan, Chu, Zhiwen, Shang, Lijun, Yu, Xiaoqi, Yu, Kangkang and Xu, Wenming (2023) Dissecting sperm mitochondrial G-quadruplex structures using a fluorescent probe biomarker to monitor and regulate fertilization capability. ACS Sensors, 8 (6). pp. 2186-2196. ISSN 2379-3694

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Abstract / Description

To monitor the levels of mitochondrial DNA G-quadruplexes (mtDNA G4s) in spermatozoa and to explore the possibility using mtDNA G4s as a reliable marker in patients with multiple clinical insemination failures, a novel chemical TPE-mTO probe engineered in our previous work was used on both samples from the mice sperm and from patients with fertilization failure. Expression of valosin-containing protein and the zona-free hamster egg assay were used to evaluate mitophagy and human sperm penetration. RNA-sequencing was used to explore expression changes of key genes affected by mtDNA G4s. Results showed that the probe can track mtDNA G4s in spermatozoa easily and quickly with fewer backgrounds. Significantly increased mtDNA G4s were also found in patients with fertilization failure, using the flow-cytometry-based TPE-mTO probe detection method. A sperm–hamster egg penetration experiment showed that abnormal fertilization caused by increased mtDNA G4s can be effectively restored by a mitophagy inducer. This study provides a novel method for monitoring etiological biomarkers in patients with clinical infertility and treatment for patients with abnormal fertilization caused by mtDNA G4 dysfunction.

Item Type:	Article
Uncontrolled Keywords:	G-quadruplexes; mitochondria; spermatozoa; fertilization failure; mitophagy
Subjects:	500 Natural Sciences and Mathematics > 570 Life sciences; biology 600 Technology > 610 Medicine & health 600 Technology > 660 Chemical engineering
Department:	School of Human Sciences
Depositing User:	Lijun Shang
Date Deposited:	26 May 2023 09:26
Last Modified:	28 Jun 2023 14:27
URI:	https://repository.londonmet.ac.uk/id/eprint/8556

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