Adenomyosis is characterised by epithelial gland and mesenchymal stroma invasion of the uterine myometrium. Adenomyosis is an oestrogen-dependent gynaecological disease in which a number of factors, such as inflammatory molecules, prostaglandins (PGs), angiogenic factors, cell proliferation and extracellular matrix remodelling proteins, also play a role as key disease mediators. In this study, we used mice lacking both lipocalin and hematopoietic-PG D synthase (L- and H-Pgds) genes in which PGD2 is not produced to elucidate PGD2 roles in the uterus. Gene expression studied by real-time PCR and hormone dosages performed by ELISA or liquid chromatography tandem mass spectroscopy in mouse uterus samples showed that components of the PGD2 signalling pathway, both PGDS and PGD2-receptors, are expressed in the mouse endometrium throughout the oestrus cycle with some differences among uterine compartments. We showed that PGE2 production and the steroidogenic pathway are dysregulated in the absence of PGD2. Histological analysis of L/H-Pgds−/− uteri, and immunohistochemistry and immunofluorescence analyses of proliferation (Ki67), endothelial cell (CD31), epithelial cell (pan-cytokeratin), myofibroblast (α-SMA) and mesenchymal cell (vimentin) markers, identify that 6-month-old L/H-Pgds−/− animals developed adenomyotic lesions, and that disease severity increased with age. In conclusion, this study suggests that the PGD2 pathway has major roles in the uterus by protecting the endometrium against adenomyosis development. Additional experiments, using for instance transcriptomic approaches, are necessary to fully determine the molecular mechanisms that lead to adenomyosis in L/H-Pgds−/− mice and to confirm whether this strain is an appropriate model for studying the human disease.

中文翻译：

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在小鼠中，前列腺素 D2 信号传导可保护子宫内膜免受子宫腺肌病的影响

子宫腺肌病的特征是上皮腺体和间充质基质侵入子宫肌层。子宫腺肌症是一种雌激素依赖性妇科疾病，其中炎症分子、前列腺素（PGs）、血管生成因子、细胞增殖和细胞外基质重塑蛋白等多种因素也作为关键的疾病介质发挥作用。在这项研究中，我们使用缺乏脂质运载蛋白和造血-PG D 合酶（L-和 H-Pgds）基因的小鼠，其中不产生 PGD2，以阐明 PGD2 在子宫中的作用。通过实时 PCR 研究的基因表达和通过 ELISA 或液相色谱串联质谱在小鼠子宫样本中进行的激素剂量研究表明，PGD2 信号通路的成分，包括 PGDS 和 PGD2 受体，在整个发情周期的小鼠子宫内膜中表达，子宫腔之间存在一些差异。我们发现在没有 PGD2 的情况下，PGE2 的产生和类固醇生成途径失调。L/H-Pgds-/- 子宫的组织学分析，以及增殖 (Ki67)、内皮细胞 (CD31)、上皮细胞 (泛细胞角蛋白)、肌成纤维细胞 (α-SMA) 和间充质细胞 (波形蛋白) 的免疫组织化学和免疫荧光分析标记，确定 6 个月大的 L/H-Pgds-/- 动物出现子宫腺肌病病变，并且疾病严重程度随着年龄的增长而增加。总之，这项研究表明 PGD2 通路通过保护子宫内膜免受子宫腺肌病的发展而在子宫中发挥重要作用。额外的实验，例如使用转录组学方法，