Testis electroporation coupled with autophagy inhibitor to treat non-obstructive azoospermia

• Published in: Molecular therapy. Nucleic acids Vol. 30; pp. 451 - 464
• Main Authors: Wang, Liying, Liu, Chao, Wei, Huafang, Ouyang, Yingchun, Dong, Mingzhe, Zhang, Ruidan, Wang, Lina, Chen, Yinghong, Ma, Yanjie, Guo, Mengmeng, Yu, Yang, Sun, Qing-Yuan, Li, Wei
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 13.12.2022; American Society of Gene & Cell Therapy; Elsevier
• Subjects: 3-methyladenine; autophagy; electroporation; male infertility; MT: Delivery Strategies; non-obstructive azoospermia; Original; non-obstructive azoospermia; autophagy; electroporation; MT: Delivery Strategies; male infertility; 3-methyladenine
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2022.10.022

Infertility affects 10%–20% of the population in most countries, with approximately half of those cases resulting from male infertility. Although millions of infertile men are able to have children with the assistance of reproductive technology, individuals with non-obstructive azoospermia (NOA) syndrome are unable to do so because they lack functional sperm. Therefore, some other strategies for infertile NOA men are still urgently needed. Our current study uses an NOA-like mouse model to optimize microinjection and a subsequent electroporation method to test potential treatment strategies. We showed that the spermatogenetic process could be partially rescued in young Stra8-Rnf20−/− mice with microinjection and subsequent electroporation of Rnf20 plasmids into the testes. All meiotic prophase I stages could be identified, and programmed DNA double-strand break repair factors could successfully be recruited to Stra8-Rnf20−/− spermatocytes after electroporation. Moreover, by including an autophagy inhibitor in the treatment, electroporation significantly improved the spermatogenetic rescue efficiency of adult Stra8-Rnf20−/− mice. Most importantly, infertility caused by Rnf20 depletions could be overcome by electroporation coupled with intracytoplasmic sperm injection. Our studies establish a relative safe and efficient testis electroporation system and provide a promising therapeutic strategy for patients with NOA. [Display omitted] Wang et al. report that testis electroporation coupled with autophagy inhibitor could rescue the spermatogenesis process of a non-obstructive azoospermia-like mouse model. These results establish a safe and efficient testes electroporation strategy to overcome male infertility, potentially providing a way to treat individuals with NOA.