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Journal of ZheJiang University(Medical Science)  2015, Vol. 44 Issue (3): 269-277    DOI: 10.3785/j.issn.1008-9292.2015.05.06
Role of mast cells in estrogen-mediated experimental endometriosis in rats
LIN Kai-qing, ZHU Li-bo, ZHANG Xin-mei, LIN Jun
Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
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Objective: To investigate the role of mast cells in the pathogenesis of estrogen-mediated experimental endometriosis in rats. Methods: Endometriosis model was established by transplanting autologous fragments of uterus to the inner surface of the abdominal wall in 24 unpregnant female Sprague Dawley rats. The rats were divided randomly into three groups(n=8 in each group), and were injected with different doses of estrogen: high-dose group(200 μg·kg-1·d-1), low-dose group(100 μg·kg-1·d-1) and the control group(0 μg·kg-1·d-1). The ovaries were surgically removed in high-dose and low-dose groups. Four rats were sacrificed in each group at 2 and 4 weeks after surgery. Their serum estradiol levels, size of lesions, total number of mast cells and degranulations, serum TNF-α levels, expression of tryptase and NGF in tissues were analyzed and compared among groups. Results: The mean levels of serum estradiol 2 weeks and 4 weeks after model established and serum TNF-α at 4 weeks in estrogen-treated groups were significantly higher than those in control group(all P<0.05). The mean size of endometriotic lesions in the estrogen-treated groups was also significantly larger than that in the control group 2 weeks and 4 weeks after model established(all P<0.05). Meanwhile, both at week 2 and week 4, the mean ratio of degranulation/total number of mast cells by toluidine blue staining in low-dose estrogen group was significantly higher than that in the control group(P<0.05). The expression of NGF in high-dose estrogen group was significantly higher than that in the control group at week 4(P<0.05). Conclusion: Estrogen can promote the growth of endometriotic lesions and may mediate the pathogenesis of endometriosis by activating mast cells, which may be associated with increasing TNF-α and NGF levels.

Key wordsEndometriosis/pathology      Mast cells/pathology      Estrogens/pharmacology      Estrogens/administration &      dosage      Cell degranulation      Immunohistochemistry      Staining and labeling      Disease models, animal     
Received: 17 December 2014      Published: 25 May 2015
CLC:  R711.71  
Cite this article:

LIN Kai-qing, ZHU Li-bo, ZHANG Xin-mei, LIN Jun. Role of mast cells in estrogen-mediated experimental endometriosis in rats. Journal of ZheJiang University(Medical Science), 2015, 44(3): 269-277.

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目的:探讨肥大细胞在雌激素介导的大鼠子宫内膜异位症模型中的作用及相关机制。方法:取健康雌性未孕SD大鼠24只,采用自体子宫内膜移植法建立大鼠腹壁子宫内膜异位症模型,按每天肌肉注射不同剂量雌激素将大鼠随机分成3组(每组8只):大剂量组(雌激素200 μg/kg+双卵巢切除)、小剂量组(雌激素100 μg/kg+双卵巢切除)、模型对照组(仅作子宫内膜移植)。分别于造模后2周及4周后处死各组4只大鼠,采集血液和病灶组织标本,测量各组子宫内膜异位症病灶的大小,并对病灶组织进行苏木素—伊红(HE)染色观察组织形态及角蛋白和波形蛋白免疫组织化学染色以鉴定造模是否成功。用甲苯胺蓝染色法检测各组大鼠病灶组织肥大细胞总数及脱颗粒肥大细胞数,酶联免疫吸附试验测定血清肿瘤坏死因子α水平,酶免疫分析法测定血清雌二醇水平,免疫组织化学染色法检测子宫内膜异位症病灶组织类胰蛋白酶、神经生长因子的表达水平。结果:两雌激素组2周和4周时血清雌二醇水平均大于模型对照组(均P<0.05),4周时大剂量组血清肿瘤坏死因子α浓度大于模型对照组(P<0.05);两雌激素组2周和4周病灶体积均大于模型对照组(均P<0.05);无论是2周还是4周,小剂量组甲苯胺蓝染色脱颗粒/肥大细胞总数比值均高于模型对照组(均P<0.05);4周时大剂量组神经生长因子的表达大于模型对照组(P<0.05)。结论:雌激素可促进子宫内膜异位症病灶的生长,其机制可能与激活肥大细胞脱颗粒相关,而后者可能与子宫内膜异位症模型大鼠血清肿瘤坏死因子α、神经生长因子水平升高有关。

关键词: 子宫内膜异位症/病理学,  肥大细胞/病理学,  雌激素类/药理学,  雌激素类/投药和剂量,  细胞脱颗粒,  免疫组织化学,  染色与标记,  疾病模型,  动物 

[1] ZHANG G, DMITRIEVA N, LIU Y, et al. Endometriosis as a neurovascular condition: estrous variations in innervation, vascularization, and growth factor content of ectopic endometrial cysts in the rat [J]. Am J Physiol Regul Integr Comp Physiol, 2008, 294(1):R162-R171.
[2] ASANTE A, TAYLOR R N. Endometriosis: the role of neuroangiogenesis[J]. Annu Rev Physiol, 2011, 73:163-182.
[3] VERNON M W, WILSON E A. Studies on the surgical induction of endometriosis in the rat [J]. Fertil Steril, 1985, 44(5):684-694.
[4] GIUDICE L C, KAO L C. Endometriosis [J]. Lancet, 2004, 364(9447):1789-1799.
[5] ANAF V, CHAPRON C, EI NAKADI I, et al. Pain, mast cells, and nerves in peritoneal, ovarian, and deep infiltrating endometriosis [J]. Fertil Steril, 2006, 86 (5):1336-1343.
[6] MATSAZAKI S, CANIS M, DARCHA C, et al. Increased mast cell density in peritoneal endometriosis compared with eutopic endometrium with endometriosis [J]. Am J Reprod Immunol, 1998, 40(4):291-294.
[7] PAULA R J R, OLIANI A H, VAZ-OLIANI D A, et al. The intricate role of mast cell proteases and the annexin A1-FPR1 system in abdominal wall endometriosis [J]. J Mol Histol, 2015,46(1):33-43.
[8] FUJIWARA H, KONNO R, NETSU S, et al. Localization of mast cells in endometrial cysts [J]. Am J Reprod Immunol, 2004, 51(5):341-344.
[9] KEMPURAJ D, PAPADOPOULOU N, STANFORD E J, et al. Increased numbers of activated mast cells in endometriosis lesions positive for corticotropin-releasing hormone and urocortin [J]. Am J Reprod Immunol, 2004, 52(4):267-275.
[10] SUGAMATA M, IHARA T, UCHIIDE I. Increase of activated mast cells in human endometriosis [J]. Am J Reprod Immunol, 2005, 53(3):120-125.
[11] ZAITSU M, NARITA S, LAMBERT K C, et al. Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx[J]. Mol Immunol, 2007, 44(8):1977-1985.
[12] PANG X, COTREAU-BIBBO M M, SANT G R, et al. Bladder mast cell expression of high affinity oestrogen receptors in patients with interstitial cystitis [J]. Br J Urol, 1995, 75(2):154-161.
[13] JING H,WANG Z,CHEN Y.Effect of oestradiol on mast cell number and histamine level in the mammary glands of rat[J]. Anat Histol Embryol,2012,41(3):170-176.
[14] JENSEN F,WOUDWYK M,TELES A, et al. Estradiol and progesterone regulate the migration of mast cells from the periphery to the uterus and induce their maturation and degranulaton[J]. PLoS One,2010,5(12):e14409.
[15] LANLUA P, DECORTI F, GANGULA P R, et al. Female steroid hormones modulate receptors for nerve growth factor in rat dorsal root ganglia [J]. Biol Reprod, 2001, 64(1):331-338.
[16] ZHANG R J, WILD R A, OJAGO J M. Effect of tumor necrosis factor-alpha on adhesion of human endometrial stromal cells to peritoneal mesothelial cells: an in vitro system [J]. Fertil Steril, 1993, 59(6):1196-1201.
[17] BULLIMORE D W. Endometriosis is sustained by tumour necrosis factor-alpha [J]. Med Hypotheses, 2003, 60(1):84-88.
[18] EISERMANN J, GAST M J, PINEDA J, et al. Tumor necrosis factor in peritoneal fluid of women undergoing laparoscopic surgery [J]. Fertil Steril, 1988, 50(4):573-579.
[19] CALHAZ-JORGE C, COSTA A P, BARATA M, et al. Tumour necrosis factor alpha concentrations in the peritoneal fluid of infertile women with minimal or mild endometriosis are lower in patients with red lesions only than in patients without red lesions [J]. Hum Reprod, 2000, 15(6):1256-1260.
[20] BEDAIWY M A, FALCONE T, SHARMA R K, et al. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial [J]. Hum Reprod, 2002, 17(2):426-431.
[21] PIZZO A, SALMERI F M, ARDITA F V, et al. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis [J]. Gynecol Obstet Invest, 2002, 54(2):82-87.
[22] MALUTAN A M, DRUGAN T, COSTIN N, et al. Pro-inflammatory cytokines for evaluation of inflammatory status in endometriosis[J]. Cent Eur J Immunol,2015,40(1):96-102.
[23] PEZET S, MCMAHON S B. Neurotrophins: mediators and modulators of pain [J]. Annu Rev Neurosci, 2006, 29:507-538.
[24] KAJITANI T,MARUYAMA T,ASADA H, et al. Possible involvement of nerve growth factor in dysmenorrhea and dyspareunia associated with endometriosis[J]. Endocr J,2013,60(10):1155-1164.

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