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卵巢碎片化与AKT刺激以延长生育寿命

Ovarian Fragmentation and AKT Stimulation for Expansion of Fertile Lifespan.

作者信息

Vo Kim Cat Tuyen, Kawamura Kazuhiro

机构信息

Department of Obstetrics and Gynecology, Advanced Reproduction Research Center, International University of Health and Welfare, Narita, Japan.

出版信息

Front Reprod Health. 2021 Mar 2;3:636771. doi: 10.3389/frph.2021.636771. eCollection 2021.

DOI:10.3389/frph.2021.636771
PMID:36304045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9580792/
Abstract

Since the first baby was born after fertilization, the female infertility treatment has been well-developed, yielding successful outcomes. However, successful pregnancies for patients with premature ovarian insufficiency and diminished ovarian reserve are still difficult and diverse therapies have been suggested to improve the chances to have their genetically linked offspring. Recent studies demonstrated that the activation Akt pathway by using a phosphatase and tensin homolog enzyme inhibitor and a phosphatidylinositol-3 kinase stimulator can activate dormant primordial follicles in both mice and human ovaries. Subsequent researches suggested that the disruption of Hippo signaling pathway by ovarian fragmentation increased the expression of downstream growth factors and secondary follicle growth. Based on the combination of ovarian fragmentation and Akt stimulation, the activation (IVA) approach has resulted in successful follicle growth and live births in premature ovarian insufficiency patients. The approach with disruption of Hippo signaling only was also shown to be effective for treating poor ovarian responders with diminishing ovarian reserve, including advanced age women and cancer patients undergoing sterilizing treatments. This review aims to summarize the effectiveness of ovarian fragmentation and Akt stimulation on follicle growth and the potential of IVA in extending female fertile lifespan.

摘要

自首例体外受精婴儿诞生以来，女性不孕症治疗已得到充分发展并取得了成功。然而，对于卵巢早衰和卵巢储备功能减退的患者来说，成功受孕仍然困难重重，人们提出了多种治疗方法以提高她们生育有血缘关系后代的几率。最近的研究表明，使用磷酸酶和张力蛋白同源物酶抑制剂以及磷脂酰肌醇-3激酶刺激剂激活Akt信号通路，可以激活小鼠和人类卵巢中休眠的原始卵泡。随后的研究表明，卵巢分割破坏Hippo信号通路可增加下游生长因子的表达并促进次级卵泡生长。基于卵巢分割和Akt刺激的联合作用，激活（IVA）方法已使卵巢早衰患者成功实现卵泡生长并诞生活婴。仅破坏Hippo信号通路的方法也被证明对治疗卵巢储备功能减退的卵巢反应不良患者有效，包括高龄女性和接受绝育治疗的癌症患者。本综述旨在总结卵巢分割和Akt刺激对卵泡生长的有效性以及IVA在延长女性生育寿命方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5da/9580792/4639a13e9f3d/frph-03-636771-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5da/9580792/8af1e6748b1a/frph-03-636771-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5da/9580792/bd4668ede43d/frph-03-636771-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5da/9580792/4639a13e9f3d/frph-03-636771-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5da/9580792/8af1e6748b1a/frph-03-636771-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5da/9580792/bd4668ede43d/frph-03-636771-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5da/9580792/4639a13e9f3d/frph-03-636771-g0003.jpg

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本文引用的文献

1
fragmentation of ovarian tissue activates primordial follicles through the Hippo pathway.卵巢组织的碎片化通过Hippo信号通路激活原始卵泡。
Hum Reprod Open. 2020 Nov 16;2020(4):hoaa048. doi: 10.1093/hropen/hoaa048. eCollection 2020.
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Surgical approaches of drug-free in vitro activation and laparoscopic ovarian incision to treat patients with ovarian infertility.无药物辅助的体外激活和腹腔镜卵巢切开术治疗卵巢性不孕患者的手术方法。
Fertil Steril. 2020 Dec;114(6):1355-1357. doi: 10.1016/j.fertnstert.2020.07.029. Epub 2020 Sep 6.
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Hippo signaling disruption and ovarian follicle activation in infertile patients.
Front Aging. 2023 Apr 11;4:1158510. doi: 10.3389/fragi.2023.1158510. eCollection 2023.
Hippo 信号通路阻断与不孕患者的卵泡激活。
Fertil Steril. 2020 Sep;114(3):458-464. doi: 10.1016/j.fertnstert.2020.07.031. Epub 2020 Aug 8.
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Effect of sphingosine-1-phosphate on activation of dormant follicles in murine and human ovarian tissue.鞘氨醇-1-磷酸对小鼠和人类卵巢组织中休眠卵泡激活的影响。
Mol Hum Reprod. 2020 May 15;26(5):301-311. doi: 10.1093/molehr/gaaa022.
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Drug-free in-vitro activation of follicles and fresh tissue autotransplantation as a therapeutic option in patients with primary ovarian insufficiency.在原发性卵巢功能不全患者中，作为一种治疗选择，进行无药物的体外卵泡激活和新鲜组织自体移植。
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Interaction between PI3K/AKT and Hippo pathways during in vitro follicular activation and response to fragmentation and chemotherapy exposure using a mouse immature ovary model.在使用小鼠未成熟卵巢模型进行体外卵泡激活以及对碎片化和化疗暴露的反应过程中，PI3K/AKT 和 Hippo 通路之间的相互作用。
Biol Reprod. 2020 Mar 13;102(3):717-729. doi: 10.1093/biolre/ioz215.
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Drug-free in-vitro activation of follicles for infertility treatment in poor ovarian response patients with decreased ovarian reserve.在卵巢储备功能下降的卵巢反应不良患者中，为不孕治疗进行无药物的体外卵泡激活。
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The Hippo pathway integrates PI3K-Akt signals with mechanical and polarity cues to control tissue growth.Hippo 通路将 PI3K-Akt 信号与机械和极性线索整合在一起，以控制组织生长。
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Evidence that biopsying, fragmentation and auto-transplantation of ovarian tissue should be abandoned as a treatment of diminished ovarian reserve.有证据表明，卵巢组织活检、分割及自体移植作为一种治疗卵巢储备功能减退的方法应被摒弃。
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