背景:据推测,早发性子宫内膜异位症的起源可能来自新生儿子宫血液(NUB)中的子宫内膜间充质干细胞(eMSCs)。没有关于NUB/新生儿子宫内膜与早发性子宫内膜异位症发展之间可能联系的机制基础的信息。在这项研究中,我们进行了一系列实验,以阐明NUB和/或新生儿子宫内膜与早发性子宫内膜异位症发展之间的机制联系。
方法:我们回顾性收集了死后新生儿子宫内膜(n=15)和前瞻性收集的女婴NUB(n=18),用于分析包括eMSCs在内的不同生物学标志物。对新生儿子宫内膜进行免疫组织化学分析以检查卵巢类固醇受体(ER/PGR)的表达模式,蜕膜化(催乳素,IGFBP1),预蜕膜化(GlycodelinA,α-SMA),增殖(Ki-67指数),血管分布(CD31+细胞),免疫活性CD68+,CD45+,CD56+细胞和一些推定的eMSC标志物。细胞转移方法和免疫细胞化学用于研究NUB中的eMSCs和/或子宫内膜细胞。
结果:死后新生儿子宫内膜的免疫组织化学分析显示对ER/PGR的可变染色反应,蜕膜标记,和大量的增殖和血管生成活性。在新生儿和成人子宫内膜中均发现了Glycodelin-A的中度至强免疫表达。CD56+的组织浸润,新生儿子宫内膜CD45+和CD68+免疫活性细胞明显低于成人子宫内膜(p=0.0003,p<0.0001,p=0.034)。在NUB中未检测到eMSCs甚至子宫内膜细胞。然而,在新生儿子宫内膜中发现了一些eMSCs表型(CD90/CD105)的可变表达.
结论:根据我们的系列实验,我们没有发现任何支持NUB在早发性子宫内膜异位症中的作用的证据。新生儿子宫内膜显示卵巢类固醇受体的可变表达,判定化,和大量的增殖和血管生成活性。作为一种替代机制,新生儿子宫内膜中免疫活性细胞的组织积累明显减少,这可能解释了ER+和PGR+细胞进入骨盆后存活的原因,以及随着卵巢功能的发生而发生早期子宫内膜异位症.未来的大样本量研究和改良技术工具的应用是必要的,以检验NUB假设并阐明其生物学或临床意义。
背景:不适用。
BACKGROUND: It has been hypothesized that the origin of early-onset endometriosis could be from endometrial mesenchymal stem cells (eMSCs) in neonatal uterine blood (NUB). There is no information on the possible mechanistic basis linking an association between NUB/neonatal endometrium and development of early-onset endometriosis. In this study we performed a series of experiments to clarify the mechanistic link between NUB and/or neonatal endometrium and development of early-onset endometriosis.
METHODS: We retrospectively collected postmortem neonatal endometria (n = 15) and prospectively collected NUB (n = 18) of female babies for the analysis of different biological markers including eMSCs. Immunohistochemical analysis of neonatal endometria was performed to examine the expression patterns of ovarian steroid receptors (ER/PGR), decidualization (prolactin, IGFBP1), pre-decidualization (Glycodelin A, α-SMA), proliferation (Ki-67 index), vascularity (CD31 + cells), immunocompetent CD68+, CD45+, CD56 + cells and some putative markers of eMSCs. Cell transfer method and immunocytochemistry were used to investigate the eMSCs and/or endometrial cells in NUB.
RESULTS: Immunohistochemical analysis of postmortem neonatal endometria revealed variable staining response to ER/PGR, decidual markers, and substantial proliferative and angiogenic activity. A moderate to strong immunoexpression of Glycodelin-A was found in both neonatal and adult endometria. The tissue infiltration of CD56+, CD45 + and CD68 + immunocompetent cells was significantly low in neonatal endometria than that in adult endometria (p = 0.0003, p < 0.0001, p = 0.034, respectively). No eMSCs or even endometrial cells were detected in NUB. However, a variable expression of some phenotypes of eMSCs (CD90/CD105) was found in neonatal endometria.
CONCLUSIONS: Based on our serial experiments we did not find any supporting evidence for the role of NUB in early-onset endometriosis. Neonatal endometria showed variable expression of ovarian steroid receptors, decidualization, and a substantial amount of proliferative and angiogenic activity. As an alternative mechanism, a significantly less tissue accumulation of immunocompetent cells in neonatal endometria may explain the survival of ER + and PGR + cells should they make entry into the pelvis and consequent development of early endometriosis with the onset of ovarian function. Future study with large sample size and application of modified technological tools is warranted to test the NUB hypothesis and to clarify their biological or clinical significance.
BACKGROUND: not applicable.