自然卵巢和人工卵巢保存生育力的研究进展
作者:
基金项目:

上海市肿瘤能量治疗技术与器械协同创新中心


Fertility preservation through natural and artificial ovaries:a review
Author:
  • 摘要
  • | |
  • 访问统计
  • |
  • 参考文献 [71]
  • |
  • 相似文献 [20]
  • | | |
  • 文章评论
    摘要:

    卵巢组织冷冻保存(ovarian tissue cryopreservation, OTC)是青春期前女性和需要立即化疗的年轻女性保存生育力的唯一选择。卵巢组织移植已被证明可以恢复激素周期和生育能力。对于某些类型的癌症患者,卵巢组织冷冻后移植有将恶性细胞和移植组织一起重新植入的风险。因此,人工卵巢作为一种创新的互补方案,能够实现离体卵泡正常发育、卵母细胞成熟和排卵,可以部分恢复内分泌的功能。文中总结了自然卵巢组织保存生育力的方法,主要包括卵巢组织慢速冷冻、玻璃化冷冻,以及水凝胶包封卵巢组织。同时对于人工卵巢组织保存生育力进行综述,主要包括水凝胶包封卵泡、支架构建卵巢微组织和3D打印的工程策略。最后对于卵巢组织保存生育力目前面临的问题和挑战进行分析,并展望了未来的发展趋势,为卵巢组织生育力保存的应用提供参考。

    Abstract:

    Ovarian tissue cryopreservation (OTC) is currently the exclusive choice for preserving fertility in both young girls before reaching puberty and young women who require immediate chemotherapy. Ovarian tissue transplantation has proven to be effective in restoring hormonal cycles and fertility. However, in certain cancer cases, there is a potential risk of inadvertently reintroducing malignant cells when transplanting cryopreserved ovarian tissue. Therefore, the use of an artificial ovary as an innovative and complementary approach allows for the development of isolated follicles, facilitates oocyte maturation and ovulation, and can partially restore endocrine function. This paper presents a comprehensive overview of techniques used to preserve fertility in natural ovarian tissues, including slow freezing, vitrification and hydrogel encapsulation methods. Additionally, it reviews fertility preservation techniques for artificial ovarian tissues, such as strategies involving hydrogel-encapsulated follicle, scaffolding for constructing ovarian microtissues, and 3D printing engineering. Lastly, this article explores current challenges and difficulties encountered in preserving ovarian tissue fertility, while also anticipating future trends in development, making it a valuable reference for the implementation of ovarian tissue fertility preservation.

    参考文献
    [1] 首都医科大学附属北京妇产医院,中国人体健康科技促进会生育力保护与保存专业委员会,阮祥燕. 卵巢组织冻存移植技术规范团体标准[J]. 中国全科医学, 2023, 26(23): 2836-2841.Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Preservation of China Association for the Promotion of Health Science, Technology, RUAN XY. Specification for ovarian tissue cryopreservation and transplantation[J]. Chinese General Practice, 2023, 26(23): 2836-2841 (in Chinese).
    [2] TRAPPHOFF T, DIETERLE S. Cryopreservation of ovarian and testicular tissue and the influence on epigenetic pattern[J]. International Journal of Molecular Sciences, 2023, 24(13): 11061.
    [3] DOLMANS MM. From isolated follicles to the artificial ovary: why and how?[J]. Current Opinion in Endocrine and Metabolic Research, 2021, 18: 62-68.
    [4] PENG X, CHENG C, ZHANG XM, HE XL, LIU Y. Design and application strategies of natural polymer biomaterials in artificial ovaries[J]. Annals of Biomedical Engineering, 2023, 51(3): 461-478.
    [5] HOPKINS TIR, BEMMER VL, FRANKS S, DUNLOP C, HARDY K, DUNLOP IE. Micromechanical mapping of the intact ovary interior reveals contrasting mechanical roles for follicles and stroma[J]. Biomaterials, 2021, 277: 121099.
    [6] PASCOLETTI G, Di NARDO M, FRAGOMENI G, BARBATO V, CAPRIGLIONE T, GUALTIERI R, TALEVI R, CATAPANO G, ZANETTI EM. Dynamic characterization of the biomechanical behaviour of bovine ovarian cortical tissue and its short-term effect on ovarian tissue and follicles[J]. Materials, 2020, 13(17): 3759.
    [7] STEWART S, OU W, ARANDA-ESPINOZA H, RAHAMAN SO, HE XM. Micromechanical characterizations and viscoelastic modeling reveal elastic and viscoelastic heterogeneities in ovarian tissue and the significant viscoelastic contribution to the apparent elastic modulus determined by AFM indentation[J]. Acta Biomaterialia, 2023, 168: 286-297.
    [8] SHAH JS, SABOUNI R, CAYTON VAUGHT KC, OWEN CM, ALBERTINI DF, SEGARS JH. Biomechanics and mechanical signaling in the ovary: a systematic review[J]. Journal of Assisted Reproduction and Genetics, 2018, 35(7): 1135-1148.
    [9] RUAN XY. Chinese society of gynecological endocrinology affiliated to the international society of gynecological endocrinology guideline for ovarian tissue cryopreservation and transplantation[J]. Gynecological Endocrinology: the Official Journal of the International Society of Gynecological Endocrinology, 2018, 34(12): 1005-1010.
    [10] SCHALLMOSER A, EINENKEL R, FÄRBER C, EMRICH N, JOHN J, SÄNGER N. The effect of high-throughput vitrification of human ovarian cortex tissue on follicular viability: a promising alternative to conventional slow freezing?[J]. Archives of Gynecology and Obstetrics, 2023, 307(2): 591-599.
    [11] GOSDEN RG, BAIRD DT, WADE JC, WEBB R. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at −196 ℃[J]. Human Reproduction, 1994, 9(4): 597-603.
    [12] OKTAY K, KARLIKAYA G. Ovarian function after transplantation of frozen, banked autologous ovarian tissue[J]. New England Journal of Medicine, 2000, 342(25): 1919.
    [13] OKTAY K, ECONOMOS K, KAN M, RUCINSKI J, VEECK L, ROSENWAKS Z. Endocrine function and oocyte retrieval after autologous transplantation of ovarian cortical strips to the forearm[J]. JAMA, 2001, 286(12): 1490.
    [14] DONNEZ J, DOLMANS MM, DEMYLLE D, JADOUL P, PIRARD C, SQUIFFLET J, MARTINEZ-MADRID B, van LANGENDONCKT A. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue[J]. Lancet (London, England), 2004, 364(9443): 1405-1410.
    [15] MEIROW D, LEVRON J, ELDAR-GEVA T, HARDAN I, FRIDMAN E, ZALEL Y, SCHIFF E, DOR J. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy[J]. New England Journal of Medicine, 2005, 353(3): 318-321.
    [16] KHATTAK H, MALHAS R, CRACIUNAS L, AFIFI Y, AMORIM CA, FISHEL S, SILBER S, GOOK D, DEMEESTERE I, BYSTROVA O, LISYANSKAYA A, MANIKHAS G, LOTZ L, DITTRICH R, COLMORN LB, MACKLON KT, HJORTH IMD, KRISTENSEN SG, GALLOS I, COOMARASAMY A. Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis[J]. Human Reproduction Update, 2022, 28(3): 400-416.
    [17] 申敬, 刘宝林, 李维杰, 周新丽, 王建信. 生育力保存领域冷冻载体的研究进展[J]. 制冷技术, 2023, 43(3): 78-85.SHEN J, LIU BL, LI WJ, ZHOU XL, WANG JX. Research progress of frozen carrier in fertility preservation[J]. Chinese Journal of Refrigeration Technology, 2023, 43(3): 78-85 (in Chinese).
    [18] BARBATO V, GUALTIERI R, CAPRIGLIONE T, PALLOTTA MM, BRAUN S, DI NARDO M, COSTANZO V, FERRARO R, CATAPANO G, TALEVI R. Slush nitrogen vitrification of human ovarian tissue does not alter gene expression and improves follicle health and progression in long-term in vitro culture[J]. Fertility and Sterility, 2018, 110(7): 1356-1366.
    [19] DOLMANS MM, von WOLFF M, POIROT C, DIAZ-GARCIA C, CACCIOTTOLA L, BOISSEL N, LIEBENTHRON J, PELLICER A, DONNEZ J, ANDERSEN CY. Transplantation of cryopreserved ovarian tissue in a series of 285 women: a review of five leading European centers[J]. Fertility and Sterility, 2021, 115(5): 1102-1115.
    [20] BEHL S, JOSHI VB, LARSON NB, YOUNG MC, BILAL M, WALKER DL, KHAN Z, GRANBERG CF, CHATTHA A, ZHAO YL. Vitrification versus slow freezing of human ovarian tissue: a systematic review and meta-analysis of histological outcomes[J]. Journal of Assisted Reproduction and Genetics, 2023, 40(3): 455-464.
    [21] LEE S, RYU KJ, KIM B, KANG D, KIM YY, KIM T. Comparison between slow freezing and vitrification for human ovarian tissue cryopreservation and xenotransplantation[J]. International Journal of Molecular Sciences, 2019, 20(13): 3346.
    [22] KOMETAS M, CHRISTMAN GM, KRAMER J, RHOTON-VLASAK A. Methods of ovarian tissue cryopreservation: is vitrification superior to slow freezing?—ovarian tissue freezing methods[J]. Reproductive Sciences, 2021, 28(12): 3291-3302.
    [23] 国际妇科内分泌学会中国妇科内分泌学分会及共识专家. 卵巢组织冻存与移植中国专家共识[J].中国临床医生杂志, 2018, 46(4): 496-500.Chinese Society of Gynecological Endocrinology Affiliated to International Society of Gynecological Endocrinology (CSGE-ISGE) and Expert Consensus group. Ovarian tissue cryopreservation and transplantation: the first chinese expert consensus[J]. Journal of Chinese Clinical Medicine, 2018, 46(4): 496-500 (in Chinese).
    [24] DIAZ AA, KUBO HN, HANDA N, HANNA M, LARONDA MM. A systematic review of ovarian tissue transplantation outcomes by ovarian tissue processing size for cryopreservation[J]. Frontiers in Endocrinology, 2022, 13: 918899.
    [25] ARAV A, PATRIZIO P. Techniques of cryopreservation for ovarian tissue and whole ovary[J]. Clinical Medicine Insights Reproductive Health, 2019, 13: 1179558119884945.
    [26] HOSSAY C, DONNEZ J, DOLMANS MM. Whole ovary cryopreservation and transplantation: a systematic review of challenges and research developments in animal experiments and humans[J]. Journal of Clinical Medicine, 2020, 9(10): 3196.
    [27] ZHANG JM, SHENG Y, CAO YZ, WANG HY, CHEN ZJ. Cryopreservation of whole ovaries with vascular pedicles: vitrification or conventional freezing?[J]. Journal of Assisted Reproduction and Genetics, 2011, 28(5): 445-452.
    [28] HENRY L, LABIED S, FRANSOLET M, KIRSCHVINK N, BLACHER S, NOEL A, FOIDART JM, NISOLLE M, MUNAUT C. Isoform 165 of vascular endothelial growth factor in collagen matrix improves ovine cryopreserved ovarian tissue revascularisation after xenotransplantation in mice[J]. Reproductive Biology and Endocrinology: RB&E, 2015, 13: 12.
    [29] SHIKANOV A, ZHANG Z, XU M, SMITH RM, RAJAN A, WOODRUFF TK, SHEA LD. Fibrin encapsulation and vascular endothelial growth factor delivery promotes ovarian graft survival in mice[J]. Tissue Engineering Part A, 2011, 17(23/24): 3095-3104.
    [30] DAY JR, DAVID A, CICHON AL, KULKARNI T, CASCALHO M, SHIKANOV A. Immunoisolating poly(ethylene glycol) based capsules support ovarian tissue survival to restore endocrine function[J]. Journal of Biomedical Materials Research Part A, 2018, 106(5): 1381-1389.
    [31] DAY JR, DAVID A, LONG C, BUSHNELL GG, WOODRUFF TK, SHEA LD, SHIKANOV A. Immuno-isolating dual poly(ethylene glycol) capsule prevents cancer cells from spreading following mouse ovarian tissue auto-transplantation[J]. Regenerative Medicine Frontiers, 2019(1): e190006.
    [32] THUWANUT P, COMIZZOLI P, PIMPIN A, SRITURAVANICH W, SEREEPAPONG W, PRUKSANANONDA K, TAWEEPOLCHAROEN C, TUNTIVIRIYAPUN P, SUEBTHAWINKUL C, SIRAYAPIWAT P. Influence of hydrogel encapsulation during cryopreservation of ovarian tissues and impact of post-thawing in vitro culture systems in a research animal model[J]. Clinical and Experimental Reproductive Medicine, 2021, 48(2): 111-123.
    [33] DOLMANS MM, DONNEZ J, CACCIOTTOLA L. Fertility preservation: the challenge of freezing and transplanting ovarian tissue[J]. Trends in Molecular Medicine, 2021, 27(8): 777-791.
    [34] RONESS H, MEIROW D. FERTILITY PRESERVATION: follicle reserve loss in ovarian tissue transplantation[J]. Reproduction (Cambridge, England), 2019, 158(5): F35-F44.
    [35] CACCIOTTOLA L, DONNEZ J, DOLMANS MM. Ovarian tissue damage after grafting: systematic review of strategies to improve follicle outcomes[J]. Reproductive Biomedicine Online, 2021, 43(3): 351-369.
    [36] LEONEL ECR, LUCCI CM, AMORIM CA. Cryopreservation of human ovarian tissue: a review[J]. Transfusion Medicine and Hemotherapy: Offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie, 2019, 46(3): 173-181.
    [37] ANDERSEN ST, PORS SE, La COUR POULSEN L, COLMORN LB, MACKLON KT, ERNST E, HUMAIDAN P, ANDERSEN CY, KRISTENSEN SG. Ovarian stimulation and assisted reproductive technology outcomes in women transplanted with cryopreserved ovarian tissue: a systematic review[J]. Fertility and Sterility, 2019, 112(5): 908-921.
    [38] TANAKA A, NAKAMURA H, TABATA Y, FUJIMORI Y, KUMASAWA K, KIMURA T. Effect of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogels on frozen-thawed human ovarian tissue in a xenograft model[J]. Journal of Obstetrics and Gynaecology Research, 2018, 44(10): 1947-1955.
    [39] RAJABI Z, ALIAKBARI F, YAZDEKHASTI H. Female fertility preservation, clinical and experimental options[J]. Journal of Reproduction & Infertility, 2018, 19(3): 125-132.
    [40] NAJAFI A, ASADI E, BENSON JD. Ovarian tissue cryopreservation and transplantation: a review on reactive oxygen species generation and antioxidant therapy[J]. Cell and Tissue Research, 2023, 393(3): 401-423.
    [41] LI JJ, LIU LY, WENG J, YIN TL, YANG J, FENG HL. Biological roles of l-carnitine in oocyte and early embryo development[J]. Molecular Reproduction and Development, 2021, 88(10): 673-685.
    [42] DADASHZADEH A, MOGHASSEMI S, SHAVANDI A, AMORIM CA. A review on biomaterials for ovarian tissue engineering[J]. Acta Biomaterialia, 2021, 135: 48-63.
    [43] SADR SZ, FATEHI R, MAROUFIZADEH S, AMORIM CA, EBRAHIMI B. Utilizing fibrin-alginate and matrigel-alginate for mouse follicle development in three-dimensional culture systems[J]. Biopreservation and Biobanking, 2018, 16(2): 120-127.
    [44] SUN WZ, ALEXANDER GREGORY D, TOMEH MA, ZHAO XB. Silk fibroin as a functional biomaterial for tissue engineering[J]. International Journal of Molecular Sciences, 2021, 22(3): 1499.
    [45] CHITI MC, DOLMANS MM, MORTIAUX L, ZHUGE F, OUNI E, SHAHRI PAK, van RUYMBEKE E, CHAMPAGNE SD, DONNEZ J, AMORIM CA. A novel fibrin-based artificial ovary prototype resembling human ovarian tissue in terms of architecture and rigidity[J]. Journal of Assisted Reproduction and Genetics, 2018, 35(1): 41-48.
    [46] WU T, GAO YY, SU J, TANG XN, CHEN Q, MA LW, ZHANG JJ, WU JM, WANG SX. Three-dimensional bioprinting of artificial ovaries by an extrusion-based method using gelatin-methacryloyl bioink[J]. Climacteric: the Journal of the International Menopause Society, 2022, 25(2): 170-178.
    [47] CHEN HX, XUE LQ, GONG GD, PAN JZ, WANG XL, ZHANG YY, GUO JL, QIN L. Collagen-based materials in reproductive medicine and engineered reproductive tissues[J]. Journal of Leather Science and Engineering, 2022, 4(1): 1-15.
    [48] JIANG F, XU XW, CHEN FQ, WENG HF, CHEN J, RU Y, XIAO Q, XIAO AF. Extraction, modification and biomedical application of agarose hydrogels: a review[J]. Marine Drugs, 2023, 21(5): 299.
    [49] HASSANPOUR A, TALAEI-KHOZANI T, KARGAR- ABARGHOUEI E, RAZBAN V, VOJDANI Z. Decellularized human ovarian scaffold based on a sodium lauryl ester sulfate (SLES)-treated protocol, as a natural three-dimensional scaffold for construction of bioengineered ovaries[J]. Stem Cell Research & Therapy, 2018, 9(1): 1-13.
    [50] JAMALZAEI P, VALOJERDI MR, MONTAZERI L, BAHARVAND H. Applicability of hyaluronic acid-alginate hydrogel and ovarian cells for in vitro development of mouse preantral follicles[J]. Cell Journal, 2020, 22(suppl 1): 49-60.
    [51] JAFARI H, DADASHZADEH A, MOGHASSEMI S, ZAHEDI P, AMORIM CA, SHAVANDI A. Ovarian cell encapsulation in an enzymatically crosslinked silk-based hydrogel with tunable mechanical properties[J]. Gels, 2021, 7(3): 138.
    [52] TOMASZEWSKI CE, CONSTANCE E, LEMKE MM, ZHOU H, PADMANABHAN V, ARNOLD KB, SHIKANOV A. Adipose-derived stem cell-secreted factors promote early stage follicle development in a biomimetic matrix[J]. Biomaterials Science, 2019, 7(2): 571-580.
    [53] RAFFEL N, DITTRICH R, BÄUERLE T, SEYLER L, FATTAHI A, HOFFMANN I, LEAL-EGAÑA A, BECKMANN MW, BOCCACCINI AR, LIVERANI L. Novel approach for the assessment of ovarian follicles infiltration in polymeric electrospun patterned scaffolds[J]. PLoS One, 2019, 14(4): e0215985.
    [54] REDDY MSB, PONNAMMA D, CHOUDHARY R, SADASIVUNI KK. A comparative review of natural and synthetic biopolymer composite scaffolds[J]. Polymers, 2021, 13(7): 1105.
    [55] ZHANG JP, YANG SB, YANG X, XI ZH, ZHAO L, CEN L, LU EY, YANG Y. Novel fabricating process for porous polyglycolic acid scaffolds by melt-foaming using supercritical carbon dioxide[J]. ACS Biomaterials Science & Engineering, 2018, 4(2): 694-706.
    [56] ASADUZZMAN M, CUI XL, ZHANG H, YOUNG F. Three dimensional in vitro culture of murine secondary follicles in a defined synthetic matrix[J]. Journal of Biomaterials and Nanobiotechnology, 2018, 9(3): 244-262.
    [57] XIAO S, COPPETA JR, ROGERS HB, ISENBERG BC, ZHU J, OLALEKAN SA, McKINNON KE, DOKIC D, RASHEDI AS, HAISENLEDER DJ, MALPANI SS, ARNOLD-MURRAY CA, CHEN KW, JIANG MY, BAI L, NGUYEN CT, ZHANG JY, LARONDA MM, HOPE TJ, MANIAR KP, et al. A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle[J]. Nature Communications, 2017, 8: 14584.
    [58] CHOI JK, AGARWAL P, HUANG HS, ZHAO ST, HE XM. The crucial role of mechanical heterogeneity in regulating follicle development and ovulation with engineered ovarian microtissue[J]. Biomaterials, 2014, 35(19): 5122-5128.
    [59] HE XM. Microfluidic encapsulation of ovarian follicles for 3D culture[J]. Annals of Biomedical Engineering, 2017, 45(7): 1676-1684.
    [60] AZIZ A, FU MJ, DENG J, GENG CY, LUO Y, LIN BC, YU XH, LIU B. A microfluidic device for culturing an encapsulated ovarian follicle[J]. Micromachines, 2017, 8(11): 335.
    [61] PICTON HM. Therapeutic potential of in vitro-derived oocytes for the restoration and treatment of female fertility[J]. Annual Review of Animal Biosciences, 2022, 10: 281-301.
    [62] BABALIARI E, RANELLA A, STRATAKIS E. Microfluidic systems for neural cell studies[J]. Bioengineering, 2023, 10(8): 902.
    [63] 杨加敏, 胥义, 党航宇, 韩恒鑫. 组织器官脱细胞支架的制备及研究进展[J]. 生物工程学报, 2022, 38(6): 2169-2186.YANG JM, XU Y, DANG HY, HAN HX. Preparation of tissue and organ decellularized scaffolds: a review[J]. Chinese Journal of Biotechnology, 2022, 38(6): 2169-2186 (in Chinese).
    [64] LARONDA MM, JAKUS AE, WHELAN KA, WERTHEIM JA, SHAH RN, WOODRUFF TK. Initiation of puberty in mice following decellularized ovary transplant[J]. Biomaterials, 2015, 50: 20-29.
    [65] LIU WY, LIN SG, ZHUO RY, XIE YY, PAN W, LIN XF, SHEN FX. Xenogeneic decellularized scaffold: a novel platform for ovary regeneration[J]. Tissue Engineering Part C, Methods, 2017, 23(2): 61-71.
    [66] WU T, GAO YY, TANG XN, ZHANG JJ, WANG SX. Construction of artificial ovaries with decellularized porcine scaffold and its elicited immune response after xenotransplantation in mice[J]. Journal of Functional Biomaterials, 2022, 13(4): 165.
    [67] CHITI MC, DOLMANS MM, DONNEZ J, AMORIM CA. Fibrin in reproductive tissue engineering: a review on its application as a biomaterial for fertility preservation[J]. Annals of Biomedical Engineering, 2017, 45(7): 1650-1663.
    [68] FELDER S, MASASA H, ORENBUCH A, LEVAOT N, SHACHAR GOLDENBERG M, COHEN S. Reconstruction of the ovary microenvironment utilizing macroporous scaffold with affinity-bound growth factors[J]. Biomaterials, 2019, 205: 11-22.
    [69] ZMORA S, GLICKLIS R, COHEN S. Tailoring the pore architecture in 3-D alginate scaffolds by controlling the freezing regime during fabrication[J]. Biomaterials, 2002, 23(20): 4087-4094.
    [70] LARONDA MM, RUTZ AL, XIAO S, WHELAN KA, DUNCAN FE, ROTH EW, WOODRUFF TK, SHAH RN. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice[J]. Nature Communications, 2017, 8: 15261.
    [71] ZHENG JH, LIU YB, HOU CX, LI ZK, YANG SP, LIANG X, ZHOU L, GUO JB, ZHANG JK, HUANG XH. Ovary-derived decellularized extracellular matrix-based bioink for fabricating 3D primary ovarian cells-laden structures for mouse ovarian failure correction[J]. International Journal of Bioprinting, 2022, 8(3): 597.
    引证文献
    网友评论
    网友评论
    分享到微博
    发 布
引用本文

申敬,李维杰,谭佳,夏春宇,王建信,周新丽. 自然卵巢和人工卵巢保存生育力的研究进展[J]. 生物工程学报, 2024, 40(5): 1469-1485

复制
分享
文章指标
  • 点击次数:227
  • 下载次数: 759
  • HTML阅读次数: 606
  • 引用次数: 0
历史
  • 收稿日期:2023-09-24
  • 最后修改日期:2023-12-19
  • 在线发布日期: 2024-05-06
  • 出版日期: 2024-05-25
文章二维码
您是第5998212位访问者
生物工程学报 ® 2025 版权所有

通信地址:中国科学院微生物研究所    邮编:100101

电话:010-64807509   E-mail:cjb@im.ac.cn

技术支持:北京勤云科技发展有限公司