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山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (7): 48-55.doi: 10.6040/j.issn.1671-7554.0.2022.0263

• 子宫腺肌病研究专题 • 上一篇    下一篇

子宫腺肌病动物模型研究进展

王国云,潘臧钰   

  1. 山东省立医院妇科 山东大学医学融合与实践中心, 山东 济南 250021
  • 发布日期:2022-07-27
  • 通讯作者: 王国云. E-mail:wangguoy@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(82071621);山东省科技厅重大基础类项目(ZR2021ZD34)

Research progress of animal models of adenomyosis

WANG Guoyun, PAN Zangyu   

  1. Department of Gynecology, Shandong provincial Hospital;
    Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China
  • Published:2022-07-27

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摘要： 子宫腺肌病是指子宫内膜(包括腺体和间质)侵入子宫肌层生长产生的病变;主要临床症状包括月经过多、严重痛经和不孕,对患者身心健康造成很大的影响。子宫腺肌病好发于育龄期女性,但因其病因尚不明确,缺乏敏感特异的诊断办法,且治疗手段有限,导致了目前亟需对发病机制、特征性诊断、针对性治疗的深入研究。动物模型的建立及应用对上述问题的解决具有重要意义。目前研究表明子宫腺肌病非人类特有,故有可选择的实验动物,且多种雌性动物的生殖系统与人类女性生殖系统具有相似性,有利于开展机制方面的研究。就子宫腺肌病动物模型建立及应用进行综述。

关键词: 子宫腺肌病, 动物模型, 模型建立, 发病机制, 激素

Abstract: Adenomyosis refers to the pathological changes caused by the invasion of endometrium (including glands and stroma) into the myometrium. The main clinical symptoms include menorrhagia, severe dysmenorrhea and infertility, which have a serious impact on the physical and mental health of patients. Adenomyosis often occurs in women of childbearing age, but its etiology remains unclear. There is still no specific diagnostic method, and the treatment methods are limited. Researches on the pathogenesis, characteristic diagnosis and targeted treatment are urgently needed. The establishment and application of animal models are significant to solve the above problems since many studies have shown that adenomyosis is not unique to humans. The alternative experimental animals have reproductive system similar to that of human women, which is conducive to the study of mechanism. This paper reviews the establishment and application of animal model of adenomyosis.

中图分类号: 

  • R711.74
[1] Yen CF, Huang SJ, Lee CL, et al. Molecular characteristics of the endometrium in uterine adenomyosis and its biochemical microenvironment [J]. Reprod Sci, 2017, 24(10): 1346-1361.
[2] García-Solares J, Donnez J, Donnez O, et al. Pathogenesis of uterine adenomyosis: invagination or metaplasia? [J]. Fertil and Steril, 2018, 109(3): 371-379.
[3] Koike N, Tsunemi T, Uekuri C, et al. Pathogenesis and malignant transformation of adenomyosis(review)[J]. Oncol Rep, 2013, 29(3): 861-867.
[4] Aleksandrovych V, Basta P, Gil K, et al. Current facts constituting an understanding of the nature of adenomyosis[J]. Adv Clin Exp Med, 2019, 28(6): 839-846.
[5] Greaves P, White IN. Experimental adenomyosis [J]. Best Pract Res Clin Obstet Gynaecol, 2006, 20(4): 503-510.
[6] Marks J. Evolutionary tempo and phylogenetic inference based on primate karyotypes [J]. Cytogenet Cell Genet,1982, 34(3): 261-264.
[7] Hendrickx AG, Peterson PE. Perspectives on the use of the baboon in embryology and teratology research [J]. Hum Reprod Update, 1997, 3(6): 575-592.
[8] DiGiacomo RF. Gynecologic pathology in the rhesus monkey(Macaca mulatta). II. Findings in laboratory and free-ranging monkeys [J]. Vet Pathol, 1977, 14(6): 539-546.
[9] 张静怡.米索前列醇诱导恒河猴子宫腺肌病模型[D].苏州:苏州大学,2016.
[10] Barrier BF, Malinowski MJ, Dick EJ Jr, et al. Adenomyosis in the baboon is associated with primary infertility [J]. Fertil Steril, 2004, Suppl 3: 1091-1094. doi:10.1016/j.fertnstert.2003.11.065.
[11] Graham KJ, Hulst FA, Vogelnest L, et al.Uterine adenomyosis in an orang-utan(Pongo abelii/pygmaeus)[J]. Aust Vet J, 2009, 87(1): 66-69.
[12] Barrier BF, Allison J, Hubbard GB, et al. Spontaneous adenomyosis in the chimpanzee(Pan troglodytes): a first report and review of the primate literature: case report [J]. Hum Reprod, 2007, 22(6): 1714-1717.
[13] Braundmeier AG, Fazleabas AT. The non-human primate model of endometriosis: research and implications for fecundity [J]. Mol Hum Reprod, 2009, 15(10): 577-586.
[14] DHooghe TM, Kyama CM, Chai D, et al.Nonhuman primate models for translational research in endometriosis [J]. Reprod Sci, 2009, 16(2): 152-161.
[15] Hastings JM, Fazleabas AT. A baboon model for endometriosis: implications for fertility [J]. Reprod Biol and Endocrinol, 2006, 4(Suppl. 1): S7. doi:10.1186/147-7827-S1-S7.
[16] Fazleabas AT, Kim JJ, Srinivasan S, et al. Implantation in the baboon: endometrial responses [J]. Semin Reprod Endocrinol, 1999, 17(3): 257-265.
[17] DHooghe TM, Bambra CS, Farah IO, et al. High intra-abdominal pressure during laparoscopy: effects on clinical parameters and lung pathology in baboons(Papio anubis, Papio cynocephalus)[J]. Am J Obstet Gynecol, 1993, 169(5): 1352-1356.
[18] Drury JA, Parkin KL, Coyne L, et al. The dynamic changes in the number of uterine natural killer cells are specific to the eutopic but not to the ectopic endometrium in women and in a baboon model of endometriosis[J]. Reprod Biol Endocrinol, 2018, 16(1): 67. doi: 10.1186/s12958-018-0385-3.
[19] Marquardt RM, Jeong JW, Fazleabas AT. Animal models of adenomyosis [J]. Semin Reprod Med, 2020, 38(2-3): 168-178.
[20] Taylor HS, Alderman Iii M, DHooghe TM, et al. Effect of simvastatin on baboon endometriosis [J]. Biol Reprod, 2017, 97(1): 32-38.
[21] Nagasawa H, Kusakawa S. Relationship between incidence and onset age of mammary tumours and uterine adenomyosis in four strains of mice: comparison with the findings of 40 generations previously[J]. In Vivo, 2001, 15(4): 345-349.
[22] Kida H. Histological analysis of spontaneous adenomyosis-like changes in recombinant inbred mouse uterus(SMXA mouse)-a novel animal model for adenomyosis [J]. Nihon Sanka Fujinka Gakkai Zasshi, 1994, 46(4): 323-330.
[23] Stöcklin-Gautschi NM, Guscetti F, Reichler IM, et al. Identification of focal adenomyosis as a uterine lesion in two dogs [J]. J Small Animl Pract, 2001, 42(8): 413-416.
[24] Gelberg HB, McEntee K. Pathology of the canine and feline uterine tube[J]. Vet Pathol, 1986, 23(6): 770-775.
[25] Kitawaki J, Koshiba H, Ishihara H, et al. Progesterone induction of 17beta-hydroxysteroid dehydrogenase type 2 during the secretory phase occurs in the endometrium of estrogen-dependent benign diseases but not in normal endometrium [J]. J Clin Endocrinol Metab, 2000, 85(9): 3292-3296.
[26] Ezaki K, Motoyama H, Sasaki H. Immunohistologic localization of estrone sulfatase in uterine endometrium and adenomyosis [J]. Obstet Gynecol, 2001, 98(5 Pt 1): 815-819.
[27] Kitawaki J, Noguchi T, Amatsu T, et al. Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in human endometriotic and adenomyotic tissues but not in normal endometrium [J]. Biol Reprod, 1997, 57(3): 514-519.
[28] Mehasseb MK, Panchal R, Taylor AH, et al. Estrogen and progesterone receptor isoform distribution through the menstrual cycle in uteri with and without adenomyosis [J]. Fertil Steril, 2011, 95(7): 2228-2235.
[29] Lipschutz A, Iglesias R, Panasevich VI, et al. Pathological changes induced in the uterus of mice with the prolonged administration of progesterone and 19-nor-contraceptives [J]. Br J Cancer, 1967, 21(1): 160-165.
[30] Ostrander PL, Mills KT, Bern HA, et al. Long-term responses of the mouse uterus to neonatal diethylstilbestrol treatment and to later sex hormone exposure [J]. J Natl Cancer Inst, 1985, 74(1): 121-135.
[31] Habiba M. The animal model of adenomyosis [M]. Cham: Springer International Publishing, 2016.
[32] Danilovich N, Roy I, Sairam MR. Emergence of uterine pathology during accelerated biological aging in FSH receptor-haplo insufficient mice [J]. Endocrinology, 2002, 143(9): 3618-3627.
[33] Huang TS, Chen YJ, Chou TY, et al. Oestrogen-induced angiogenesis promotes adenomyosis by activating the Slug-VEGF axis in endometrial epithelial cells [J]. J Cell Mol Med, 2014, 18(7): 1358-1371.
[34] Singtripop T, Mori T, Park MK, et al. Development of uterine adenomyosis after treatment with dopamine antagonists in mice [J]. Life Sci, 1991, 49(3): 201-206.
[35] Sengupta P, Sharma A, Mazumdar G, et al. The possible role of fluoxetine in adenomyosis: an animal experiment with clinical correlations[J]. J Clin and Diagn Res, 2013, 7(7): 1530-1534.
[36] Mori T, Nagasawa H, Takahashi S. The induction of adenomyosis in mice by intrauterine pituitary isografts [J]. Life Sci, 1981, 29(12): 1277-1282.
[37] Łupicka M, Socha BM, Szczepańska AA, et al. Prolactin role in the bovine uterus during adenomyosis [J]. Domest Anim Endocrinol, 2017, 58: 1-13. doi:10.1016/j.domaniend.2016.07.003.
[38] Singtripop T, Mori T, Park MK, et al. Development of uterine adenomyosis after treatment with dopamine antagonists in mice [J]. Life Sci, 1991, 49(3): 201-206.
[39] Fiçicioglu C, Tekin HI, Arioglu PF, et al. A murine model of adenomyosis: the effects of hyperprolactinemia induced by fluoxetine hydrochloride, a selective serotonin reuptake inhibitor, on adenomyosis induction in Wistar albino rats [J]. Acta Eur Fertil, 1995, 26(2): 75-79.
[40] Green AR, Styles JA, Parrott EL, et al. Neonatal tamoxifen treatment of mice leads to adenomyosis but not uterine cancer [J]. Exp Toxicol Pathol, 2005, 56(4,5): 255-263.
[41] Mehasseb MK, Bell SC, Habiba MA. The effects of tamoxifen and estradiol on myometrial differentiation and organization during early uterine development in the CD1 mouse[J]. Reproduction, 2009, 138(2): 341-350.
[42] Mao X, Wang Y, Carter AV, et al. The retardation of myometrial infiltration, reduction of uterine contractility, and alleviation of generalized hyperalgesia in mice with induced adenomyosis by levo-tetrahydropalmatine(l-THP)and andrographolide [J]. Reprod Sci, 2011, 18(10): 1025-1037.
[43] Mori T, Singtripop T, Kawashima S. Animal model of uterine adenomyosis: is prolactin a potent inducer of adenomyosis in mice? [J]. Am J Obstet Gynecol, 1991, 165(1): 232-234.
[44] Zhai J, Vannuccini S, Petraglia F, et al. Adenomyosis: Mechanisms and Pathogenesis [J]. Semin Reprod Med, 2020, 38(2-03): 129-143.
[45] Takemura M, Nomura S, Kimura T, et al. Expression and localization of oxytocin receptor gene in human uterine endometrium in relation to the menstrual cycle [J]. Endocrinology, 1993, 132(4): 1830-1835.
[46] Guo SW, Mao X, Ma Q, et al. Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor(OTR)in women with symptomatic adenomyosis [J]. Fertil Steril, 2013, 99(1): 231-240.
[47] Yamashita M, Matsuda M, Mori T. Increased expression of prolactin receptor mRNA in adenomyotic uterus in mice [J]. Life Sci, 1997, 60(17): 1437-1446.
[48] 张信美,邓琳,马俊彦,等.异体垂体移植诱发ICR小鼠子宫腺肌病动物模型的建立[J].现代妇产科进展, 2007,16(4): 294-296. ZHANG Xinmei, DENG Lin, MA Junyan, et al. The development of uterine adenomyosis induced by pituitary isografting in femal ICR mice [J]. Progress in Obstetrics and Gynecology, 2007, 16(4): 294-296.
[49] 赵艳,赵晓晓,师伟,等.无创法诱发Wistar大鼠子宫腺肌病模型的建立[J].中华中医药杂志, 2021, 36(4): 1887-1891. ZHAO Yan, ZHAO Xiaoxiao, SHI Wei, et al. Establishment of Wistar rats model of adenomyosis induced by non-invasive [J]. China Journal of Traditional Chinese Medicine and Pharmacy, 2021, 36(4): 1887-1891.
[50] 饶妍妍,项双卫.子宫腺肌病动物模型建立及应用进展[J].国际生殖健康/计划生育杂志, 2010, 29(2): 116-119. RAO Yanyan, XIANG Shuangwei. The progress of animal models in adenomyosis [J]. Journal of International Reproductive, 2010,29(2): 116-119.
[51] Mori T, Nagasawa H. Alteration of the development of mammary hyper- plastic alveolar nodules and uterine adenomyosis in SHN mice by different schedules of treatment with CB-154 [J]. Acta Endocrinol(Copenh), 1984, 107(2): 245-249.
[52] Nagasawa H, Noguchi Y, Mori T, et al. Suppression of normal and pre- neoplastic mammary growth and uterine adenomyosis with reduced growth hormone level in SHN mice given monosodium glutamate neonatally [J]. Eur J Cancer and Clin Oncol, 1985, 21(12): 1547-1551.
[53] Singtripop T, Mori T, Sakamoto S, et al. Suppression of the development of uterine adenomyosis by danazol treatment in mice[J]. Life Sci, 1992, 51(14): 1119-1125.
[54] Mori T, Yamasaki S, Masui F, et al. Suppression of the development of experimentally induced uterine adenomyosis by a novel matrix metallo- proteinase Inhibitor ONO-4817 in mice [J]. Exp Biol Med(Maywood), 2001, 226(5): 429-433.
[55] 张信美,邓琳,马俊彦,等.携带丹那唑宫内节育器治疗小鼠子宫腺肌病的研究[J].浙江预防医学,2007, 19(9):1-3. ZHANG Xinmei, DENG Lin, MA Junyan, et al. Study on effectiveness of danazol-loaded intrauterine device in treating experimentally induced uterine adenomyosis in the mice[J]. Preventive Medicine, 2007, 19(9): 1-3.
[56] Zhou YF, Mori T, Kudo H, et al. Effects of angiogenesis inhibitor TNP-470on the development of uterine adenomyosis in mice [J]. Fertil Steril, 2003, Suppl 2: 788-794. doi:10.1016/S0015-0282(03)00988-9.
[57] Guo S, Lu X,Gu R, et al.Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis mode [J]. Drug Des Devel Ther, 2017, 11: 695-704. doi:10.2147/DDDT.S127889.ecollection2017.
[58] Sakamoto S, Kudo H, Kawasaki T, et al. Effects of a Chinese herbal medicine, keishi-bukuryo-gan, on the gonadal system of rats [J]. J Ethnopharmacol, 1988, 23(2-3): 151-158.
[59] Mori T, Sakamoto S, Matsuda M, et al. Suppression of spontaneous development of uterine adenomyosis and mammary hyperplastic alveolar nodules by Chinese herbal medicines in mice [J]. American J Chin Med, 1993, 21(3-4): 263-268.
[60] Suzuki-Kakisaka H, Murakami T, Hirano T, et al. Selective accumulation of PpIX and photodynamic effect after aminolevulinic acid treatment of human adenomyosis xenografts in nude mice [J]. Fertil and Steril, 2008, 90(4 Suppl): 1523-1527.
[61] Kim J, Koo BK, Knoblich JA, et al. Human organoids: model systems for human biology and medicine [J]. Nat Rev Mol Cell Biol, 2020, 21(10): 571-584.
[62] Lannagan TR, Jackstadt R, Leedham SJ, et al. Advances in colon cancer research: in vitro and animal models [J]. Curr Opin Genet Dev, 2021, 66: 50-56. doi:10.1016/j.gde.2020.12.003.
[63] Filby CE, Wyatt KA, Mortlock S, et al. Comparison of organoids from menstrual fluid and hormone-treated endometrium: novel tools for gynecological research [J]. J Pers Med, 2021, 11(12): 1314.
[64] Kopper O, de Witte CJ, Lõhmussaar K, et al. An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity [J]. Nat Med, 2019, 25(5): 838-849.
[65] Gnecco JS, Brown AT, Kan EL, et al. Physiomimetic models of adenomyosis [J]. Semin Reprod Med, 2020, 38(2-3): 179-196.
[66] Griffith LG, Swartz MA. Capturing complex 3D tissue physiology in vitro [J]. Nat Rev Mol Cell Biol, 2006, 7(3): 211-224.
[67] Juárez-Barber E, Francés-Herrero E, Corachán A, et al. Establishment of adenomyosis organoids as a preclinical model to study infertility [J]. J Pers Med,2022, 12(2): 219.
[68] 俞东红,曹华,王心睿.类器官的研究进展及应用[J].生物工程学报,2021, 37(11): 3961-3974. YU Donghong, CAO Hua, WANG Xinrui. Advances and applications of organoids: a review [J]. Chinese Journal of Biotechnology, 2021, 37(11): 3961-3974.
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