Pregnancy affects morphology of induced endometriotic lesions in a mouse model through alteration of proliferation and angiogenesis
Pregnancy affects morphology of induced endometriotic lesions in a mouse model through alteration of proliferation and angiogenesis
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DOI：
10.1016/j.ejogrb.2014.10.038
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发表时间：
2014-12-01
影响因子：
2.6
通讯作者：
Aractingi, S.
中科院分区：
文献类型：
--
作者：
Cohen, J.;Naoura, I.;Aractingi, S.
目的：已知妊娠可以缓解子宫内膜异位症的症状，也已知妊娠是影响血管和淋巴管的促血管生成条件。然而，血管生成积极参与子宫内膜异位症的发展。本研究的目的是研究妊娠对子宫内膜异位组织的影响。研究设计我们在子宫内膜异位症小鼠模型中进行了一项横断面对照与治疗研究。31只雌性C57 B16小鼠交配并怀孕，31只雌性未交配并作为对照。在随后交配或未交配的C57 B16小鼠中手术诱导腹膜内增生性病变（P组：妊娠，NP组：未妊娠）。在P小鼠妊娠的第E15.5天处死P和NP小鼠并收获病变。结果：妊娠可减轻腹膜病变的重量，降低囊性成分的比例（0.02 vs. 0.4; p < 0.001），并改变腹膜增生性病变的结构。妊娠也增加了间质和腺体组织中的细胞增殖，如P组中Ki 67阳性细胞的增加所示（腺体：19 vs. 3.9%，p < 0.001;间质：8.7 vs. 3.3%，p < 0.01）。最后，妊娠增加了乳腺癌病变的血管生成，表现为微血管密度增加（CD-31和LYVE-1染色：分别为2.2%对5.1%，p < 0.01和0.4%对0.9%，p < 0.001），通过流式细胞术评估的LYVE 1阳性细胞的数量增加（18.9 vs.4.6%，p < 0.05）和通过qRT-PCR显示的VEGF-A、-R2和-R3 RNA表达的增加（p < 0.001; p < 0.01; p < 0.05）。结论：这些具有挑战性的结果为理解子宫内膜异位症的病理生理学提供了见解，并引起了病变结构和病理学之间的相关性。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Objective: Pregnancy is known to alleviate the symptoms of endometriosis and is also known to be a pro-angiogenic condition affecting blood and lymphatic vessels. However, angiogenesis actively participates in the development of endometriosis. The objective of our study was to study the impact of pregnancy on endometriotic tissue.Study design We performed a cross-sectional, control versus treatment study in a mouse model of endometriosis. Thirty-one female C57Bl6 mice were mated and became pregnant and 31 females were not mated and served as control. Intraperitoneal endometriotic lesions were surgically induced in C57Bl6 mice which were subsequently mated or not (group P: pregnant, group NP: non-pregnant). P and NP mice were sacrificed on day E15.5 of the pregnancy of P mice and lesions were harvested. Lesions were weighed and analyzed by histology, immunohistology, flow cytometry and real-time quantitative RT-PCR (qRT-PCR).Results: Pregnancy reduced lesion weight, decreased the proportion of cystic component (0.02 vs. 0.4; p < 0.001) and modified the architecture of peritoneal endometriotic lesions. Pregnancy also increased cell proliferation in both stromal and glandular tissue as shown by the increase in Ki 67-positive cells in the P group (glandular: 19 vs. 3.9%, p < 0.001; stromal: 8.7 vs. 3.3%, p < 0.01). Finally, pregnancy increased angiogenesis in endometriotic lesions as indicated by an increased microvessel density (CD-31 and LYVE-1 stainings: respectively 2.2 vs. 5.1%, p < 0.01 and 0.4 vs. 0.9%, p < 0.001), an increased number of LYVE1 positive cells evaluated by flow cytometry (18.9 vs. 4.6%, p < 0.05) and a rise in VEGF-A, -R2 and -R3 RNA expression shown by qRT-PCR (p < 0.001; p < 0.01; p < 0.05).Conclusion: These challenging results provide insight in understanding the pathophysiology of endometriosis and evoke a correlation between lesion architecture and symptomatology. (C) 2014 Elsevier Ireland Ltd. All rights reserved.