原发性卵巢功能不全患者原始卵泡体外激活技术

doi:10.12280/gjszjk.20210343

摘要/Abstract

摘要：

原发性卵巢功能不全（POI）是女性不孕的重要原因之一,目前主要治疗方法是通过供卵途径实现生育,但由于卵源及伦理问题,导致患者面临诸多困难。原始卵泡体外激活（IVA）技术的发展为POI带来了新的治疗思路,其可通过药物或非药物手段,在体外激活Hippo信号通路、磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）信号通路、哺乳动物雷帕霉素靶蛋白复合物1（mTORC1）信号通路等卵泡发育相关信号通路,诱导原始卵泡发育后,将含有原始卵泡的卵巢组织重新植入患者体内,最终实现患者的生育目的。就POI患者原始卵泡IVA技术的研究进展进行综述,为POI的临床治疗策略提供参考。

关键词: 原发性卵巢功能不全, 卵泡, 信号传导, 不育, 卵母细胞体外成熟技术, 体外激活

Abstract:

Primary ovarian insufficiency (POI) is one of the important causes of female infertility. At present, the main treatment to realize fertility is the egg donation. However, due to egg source and ethical problems, patients need to face many difficulties. The development of in vitro follicular activation technology brings new treatment ideas for the treatment of POI. The hippopotamus signaling pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, mammalian target of rapamycin complex 1 (mTORC1) signaling pathway and other follicle development-related signaling pathways can be in vitro activated by pharmacological or non-pharmacological means, to promote primordial follicle development. The ovarian tissue containing primordial follicles will be subsequently implanted back into the patient, and patients ultimately may achieve the fertility goal. We review the research progress of IVA of primordial follicles in patients with POI, so as to provide reference for the clinical treatment strategy of POI.

Key words: Primary ovarian insufficiency, Ovarian follicle, Signal transduction, Infertility, In vitro oocyte maturation techniques, In vitro activation

宋文广, 付浩, 郭敏, 胡春秀. 原发性卵巢功能不全患者原始卵泡体外激活技术[J]. 国际生殖健康/计划生育, 2021, 40(6): 486-489.

SONG Wen-guang, FU Hao, GUO Min, HU Chun-xiu. In Vitro Activation of Primordial Follicles in Patients with Primary Ovarian Insufficiency[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(6): 486-489.

参考文献 22

[1]	Anderson RA, Amant F, Braat D, et al. ESHRE guideline: female fertility preservation[J]. Hum Reprod Open, 2020, 2020(4):hoaa052. doi: 10.1093/hropen/hoaa052. doi: 10.1093/hropen/hoaa052 pmid: 33225079
[2]	谢宝国, 卢伟英. 辅助生殖技术供卵法规合理性的伦理学思考[J]. 医学与哲学, 2018, 39(9):26-27. doi: 10.12014/j.issn.1002-0772.2018.05a.07. doi: 10.12014/j.issn.1002-0772.2018.05a.07
[3]	Li J, Kawamura K, Cheng Y, et al. Activation of dormant ovarian follicles to generate mature eggs[J]. Proc Natl Acad Sci U S A, 2010, 107(22):10280-10284. doi: 10.1073/pnas.1001198107. doi: 10.1073/pnas.1001198107 URL
[4]	Kawamura K, Cheng Y, Suzuki N, et al. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment[J]. Proc Natl Acad Sci U S A, 2013, 110(43):17474-17479. doi: 10.1073/pnas.1312830110. doi: 10.1073/pnas.1312830110 URL
[5]	Terren C, Munaut C. Molecular Basis Associated with the Control of Primordial Follicle Activation During Transplantation of Cryopreserved Ovarian Tissue[J]. Reprod Sci, 2021, 28(5):1257-1266. doi: 10.1007/s43032-020-00318-z. doi: 10.1007/s43032-020-00318-z URL
[6]	Maidarti M, Anderson RA, Telfer EE. Crosstalk between PTEN/PI3K/Akt Signalling and DNA Damage in the Oocyte: Implications for Primordial Follicle Activation, Oocyte Quality and Ageing[J]. Cells, 2020, 9(1):200. doi: 10.3390/cells9010200. doi: 10.3390/cells9010200 URL
[7]	胡立桥, 周兆才, 田伟. Hippo信号通路结构生物学研究进展[J]. 遗传, 2017, 39(7):659-674. doi: 10.16288/j.yczz.17-062. doi: 10.16288/j.yczz.17-062
[8]	李佳, 袁树晟, 曹秀萍, 等. Hippo信号通路调节卵巢物质代谢对卵巢功能影响的研究进展[J]. 上海交通大学学报(医学版), 2020, 40(11):1536-1539. doi: 10.3969/j.issn.1674-8115.2020.11.018. doi: 10.3969/j.issn.1674-8115.2020.11.018
[9]	Lee KP, Lee JH, Kim TS, et al. The Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis[J]. Proc Natl Acad Sci U S A, 2010, 107(18):8248-8253. doi: 10.1073/pnas.0912203107. doi: 10.1073/pnas.0912203107 URL
[10]	Maas K, Mirabal S, Penzias A, et al. Hippo signaling in the ovary and polycystic ovarian syndrome[J]. J Assist Reprod Genet, 2018, 35(10):1763-1771. doi: 10.1007/s10815-018-1235-0. doi: 10.1007/s10815-018-1235-0 URL
[11]	李佳. Hippo信号通路在调节卵巢生殖干细胞功能和延缓卵巢衰老中的作用[D]. 南昌:南昌大学, 2016.
[12]	Hsueh A, Kawamura K. Hippo signaling disruption and ovarian follicle activation in infertile patients[J]. Fertil Steril, 2020, 114(3):458-464. doi: 10.1016/j.fertnstert.2020.07.031. doi: 10.1016/j.fertnstert.2020.07.031 URL
[13]	Basappa J, Citir M, Zhang Q, et al. ACLY is the novel signaling target of PIP(2)/PIP(3) and Lyn in acute myeloid leukemia[J]. Heliyon, 2020, 6(5):e03910. doi: 10.1016/j.heliyon.2020.e03910. doi: 10.1016/j.heliyon.2020.e03910 URL
[14]	Jang H, Smith IN, Eng C, et al. The mechanism of full activation of tumor suppressor PTEN at the phosphoinositide-enriched membrane[J]. iScience, 2021, 24(5):102438. doi: 10.1016/j.isci.2021.102438. doi: 10.1016/j.isci.2021.102438 URL
[15]	张华, 代燕丽, 张佳伟. 原始卵泡的激活与临床应用[J]. 山东大学学报(医学版), 2018, 56(4):8-17. doi: 10.6040/j.issn.1671-7554.0.2018.019. doi: 10.6040/j.issn.1671-7554.0.2018.019
[16]	吴霜. mTOR信号通路激活剂MHY1485应用于人卵巢组织体外激活的有效性及安全性研究[D]. 上海:中国人民解放军海军军医大学, 2018.
[17]	Zhang H, Risal S, Gorre N, et al. Somatic cells initiate primordial follicle activation and govern the development of dormant oocytes in mice[J]. Curr Biol, 2014, 24(21):2501-2508. doi: 10.1016/j.cub.2014.09.023. doi: 10.1016/j.cub.2014.09.023 pmid: 25438940
[18]	Nilsson EE, Skinner MK. Kit ligand and basic fibroblast growth factor interactions in the induction of ovarian primordial to primary follicle transition[J]. Mol Cell Endocrinol, 2004, 214(1/2):19-25. doi: 10.1016/j.mce.2003.12.001. doi: 10.1016/j.mce.2003.12.001 URL
[19]	Zhai J, Yao G, Dong F, et al. In Vitro Activation of Follicles and Fresh Tissue Auto-transplantation in Primary Ovarian Insufficiency Patients[J]. J Clin Endocrinol Metab, 2016, 101(11):4405-4412. doi: 10.1210/jc.2016-1589. doi: 10.1210/jc.2016-1589 pmid: 27571179
[20]	Fàbregues F, Ferreri J, Méndez M, et al. In Vitro Follicular Activation and Stem Cell Therapy as a Novel Treatment Strategies in Diminished Ovarian Reserve and Primary Ovarian Insufficiency[J]. Front Endocrinol(Lausanne), 2020, 11:617704. doi: 10.3389/fendo.2020.617704. doi: 10.3389/fendo.2020.617704
[21]	Ferreri J, Fàbregues F, Calafell JM, et al. Drug-free in-vitro activation of follicles and fresh tissue autotransplantation as a therapeutic option in patients with primary ovarian insufficiency[J]. Reprod Biomed Online, 2020, 40(2):254-260. doi: 10.1016/j.rbmo.2019.11.009. doi: 10.1016/j.rbmo.2019.11.009 URL
[22]	Kawamura K, Ishizuka B, Hsueh A. Drug-free in-vitro activation of follicles for infertility treatment in poor ovarian response patients with decreased ovarian reserve[J]. Reprod Biomed Online, 2020, 40(2):245-253. doi: 10.1016/j.rbmo.2019.09.007. doi: 10.1016/j.rbmo.2019.09.007 URL