Juárez-Barber Elena, Francés-Herrero Emilio, Corachán Ana, Vidal Carmina, Giles Juan, Alamá Pilar, Faus Amparo, Pellicer Antonio, Cervelló Irene, Ferrero Hortensia
Fundación IVI, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, 46010 Valencia, Spain.
J Pers Med. 2022 Feb 4;12(2):219. doi: 10.3390/jpm12020219.
Adenomyosis is related to infertility and miscarriages, but so far there are no robust in vitro models that reproduce its pathological features to study the molecular mechanisms involved in this disease. Endometrial organoids are in vitro 3D models that recapitulate the native microenvironment and reproduce tissue characteristics that would allow the study of adenomyosis pathogenesis and related infertility disorders. In our study, human endometrial biopsies from adenomyosis ( = 6) and healthy women ( = 6) were recruited. Organoids were established and hormonally differentiated to recapitulate midsecretory and gestational endometrial phases. Physiological and pathological characteristics were evaluated by immunohistochemistry, immunofluorescence, qRT-PCR, and ELISA. Secretory and gestational organoids recapitulated in vivo glandular epithelial phenotype (pan-cytokeratin, Muc-1, PAS, Laminin, and Ki67) and secretory and gestational features (α-tubulin, SOX9, , , , and expression and secretion). Adenomyosis organoids showed higher expression of TGF-β2 and SMAD3 and increased gene expression of , , , and compared with control organoids. Our results demonstrate that organoids derived from endometria of adenomyosis patients and differentiated to secretory and gestational phases recapitulate native endometrial-tissue-specific features and disease-specific traits. Adenomyosis-derived organoids are a promising in vitro preclinical model to study impaired implantation and pregnancy disorders in adenomyosis and enable personalized drug screening.
子宫腺肌病与不孕和流产有关，但迄今为止，尚无强大的体外模型能够再现其病理特征以研究该疾病所涉及的分子机制。子宫内膜类器官是体外三维模型，可概括天然微环境并再现组织特征，从而有助于研究子宫腺肌病的发病机制及相关不孕疾病。在我们的研究中，招募了子宫腺肌病患者（n = 6）和健康女性（n = 6）的子宫内膜活检样本。建立类器官并进行激素分化以模拟分泌中期和妊娠期子宫内膜阶段。通过免疫组织化学、免疫荧光、qRT-PCR和ELISA评估生理和病理特征。分泌期和妊娠期类器官再现了体内腺上皮表型（泛细胞角蛋白、Muc-1、PAS、层粘连蛋白和Ki67）以及分泌期和妊娠期特征（α-微管蛋白、SOX9、 、 、 和 表达以及 分泌）。与对照类器官相比，子宫腺肌病类器官显示TGF-β2和SMAD3表达更高， 、 、 和 的基因表达增加。我们的结果表明，源自子宫腺肌病患者子宫内膜并分化为分泌期和妊娠期的类器官再现了天然子宫内膜组织特异性特征和疾病特异性特征。源自子宫腺肌病的类器官是一种很有前景的体外临床前模型，可用于研究子宫腺肌病中受损的着床和妊娠障碍，并实现个性化药物筛选。
