子宫腺肌病与不孕和流产有关,但是到目前为止,还没有强大的体外模型可以重现其病理特征来研究这种疾病的分子机制。子宫内膜类器官是体外3D模型,可概括天然微环境并重现组织特征,从而研究子宫腺肌病的发病机理和相关的不育疾病。在我们的研究中,我们招募了来自子宫腺肌病(n=6)和健康女性(n=6)的子宫内膜活检.建立了类器官并进行激素分化,以概括子宫内膜中期和妊娠期。通过免疫组织化学评估生理和病理特征,免疫荧光,qRT-PCR,和ELISA。分泌型和妊娠类器官在体内腺体上皮表型(泛细胞角蛋白,Muc-1,PAS,层粘连蛋白,和Ki67)以及分泌和妊娠特征(α-微管蛋白,SOX9,SPP1,PAEP,LIF,和17βHSD2表达和SPP1分泌)。子宫腺肌病的类器官显示TGF-β2和SMAD3的高表达和SPP1,PAEP,LIF,和17βHSD2与对照类器官相比。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概括了天然的子宫内膜组织特异性特征和疾病特异性特征。子宫腺肌病衍生的类器官是一种有前途的体外临床前模型,可用于研究子宫腺肌病中受损的植入和妊娠疾病,并实现个性化药物筛选。
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 (n = 6) and healthy women (n = 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, SPP1, PAEP, LIF, and 17βHSD2 expression and SPP1 secretion). Adenomyosis organoids showed higher expression of TGF-β2 and SMAD3 and increased gene expression of SPP1, PAEP, LIF, and 17βHSD2 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.