Mitochondrial replacement techniques to resolve mitochondrial dysfunction and ooplasmic deficiencies: where are we now?

IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY Human reproduction Pub Date : 2025-03-13 DOI:10.1093/humrep/deaf034
Jessica Subirá, María José Soriano, Luis Miguel Del Castillo, María José de Los Santos
{"title":"Mitochondrial replacement techniques to resolve mitochondrial dysfunction and ooplasmic deficiencies: where are we now?","authors":"Jessica Subirá, María José Soriano, Luis Miguel Del Castillo, María José de Los Santos","doi":"10.1093/humrep/deaf034","DOIUrl":null,"url":null,"abstract":"<p><p>Mitochondria are the powerhouses of cell and play crucial roles in proper oocyte competence, fertilization, and early embryo development. Maternally inherited mitochondrial DNA (mtDNA) mutations can have serious implications for individuals, leading to life-threatening disorders and contribute to ovarian ageing and female infertility due to poor oocyte quality. Mitochondrial replacement techniques (MRTs) have emerged as a promising approach not only to replace defective maternal mitochondria in patients carrying mtDNA mutations, but also to enhance oocyte quality and optimize IVF outcomes for individuals experiencing infertility. There are two main categories of MRT based on the source of mitochondria. In the heterologous approach, mitochondria from a healthy donor are transferred to the recipient's oocyte. This approach includes several methodologies such as germinal vesicle, pronuclear, maternal spindle, and polar body transfer. However, ethical concerns have been raised regarding the potential inheritance of third-party genetic material and the development of heteroplasmy. An alternative approach to avoid these issues is the autologous method. One promising autologous technique was the autologous germline mitochondrial energy transfer (AUGMENT), which involved isolating oogonial precursor cells from the patient, extracting their mitochondria, and then injecting them during ICSI. However, the efficacy of AUGMENT has been debated following the results of a randomized clinical trial (RCT) that demonstrated no significant benefit over conventional IVF. Recent developments have focused on novel approaches based on autologous, non-invasively derived stem cells to address infertility. While these techniques show promising results, further RCTs are necessary to establish their effectiveness and safety for clinical use. Only after robust evidence becomes available could MRT potentially become a viable treatment option for overcoming infertility and enabling patients to have genetically related embryos. This review aims to provide an overview of the current state of MRTs in addressing low oocyte quality due to mitochondrial dysfunction.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human reproduction","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/humrep/deaf034","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Mitochondria are the powerhouses of cell and play crucial roles in proper oocyte competence, fertilization, and early embryo development. Maternally inherited mitochondrial DNA (mtDNA) mutations can have serious implications for individuals, leading to life-threatening disorders and contribute to ovarian ageing and female infertility due to poor oocyte quality. Mitochondrial replacement techniques (MRTs) have emerged as a promising approach not only to replace defective maternal mitochondria in patients carrying mtDNA mutations, but also to enhance oocyte quality and optimize IVF outcomes for individuals experiencing infertility. There are two main categories of MRT based on the source of mitochondria. In the heterologous approach, mitochondria from a healthy donor are transferred to the recipient's oocyte. This approach includes several methodologies such as germinal vesicle, pronuclear, maternal spindle, and polar body transfer. However, ethical concerns have been raised regarding the potential inheritance of third-party genetic material and the development of heteroplasmy. An alternative approach to avoid these issues is the autologous method. One promising autologous technique was the autologous germline mitochondrial energy transfer (AUGMENT), which involved isolating oogonial precursor cells from the patient, extracting their mitochondria, and then injecting them during ICSI. However, the efficacy of AUGMENT has been debated following the results of a randomized clinical trial (RCT) that demonstrated no significant benefit over conventional IVF. Recent developments have focused on novel approaches based on autologous, non-invasively derived stem cells to address infertility. While these techniques show promising results, further RCTs are necessary to establish their effectiveness and safety for clinical use. Only after robust evidence becomes available could MRT potentially become a viable treatment option for overcoming infertility and enabling patients to have genetically related embryos. This review aims to provide an overview of the current state of MRTs in addressing low oocyte quality due to mitochondrial dysfunction.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
求助全文
约1分钟内获得全文 去求助
来源期刊
Human reproduction
Human reproduction 医学-妇产科学
CiteScore
10.90
自引率
6.60%
发文量
1369
审稿时长
1 months
期刊介绍: Human Reproduction features full-length, peer-reviewed papers reporting original research, concise clinical case reports, as well as opinions and debates on topical issues. Papers published cover the clinical science and medical aspects of reproductive physiology, pathology and endocrinology; including andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, early pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues.
期刊最新文献
Mitochondrial replacement techniques to resolve mitochondrial dysfunction and ooplasmic deficiencies: where are we now? The major phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), affect the function of CatSper calcium channels in human sperm. Case Report: Androgenetic/biparental chimera with two biparental cell lines leading to placental mesenchymal dysplasia: a possible novel mechanism of formation. Cumulative live birth rates of 31 478 untested embryos from 11 463 women challenge traditional recurrent implantation failure definitions. High serum estradiol levels on the day of frozen blastocyst transfer are associated with increased early miscarriage rates in artificial cycles using transdermal estrogens.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1