Yu Bo, McCartney Stephen, Strenk Susan, Valint Daniel, Liu Congzhou, Haggerty Catherine, Fredricks David N
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA.
Stanford Maternal & Child Health Research Institute, Stanford University School of Medicine, Stanford, CA.
Res Sq. 2023 May 23:rs.3.rs-2891189. doi: 10.21203/rs.3.rs-2891189/v1.
To facilitate mechanistic studies in pelvic inflammatory disease (PID) and subsequent tubal factor infertility, as well as ovarian carcinogenesis, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection. Experimental study. Academic medical and researchcenter. FT tissues were obtained from four patients after salpingectomy for benign gynecological diseases. We introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, and . The inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes. Compared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the infected organoids and those infected by . Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in infected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids. : Patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful model system to study the host-pathogen interaction during bacterial infection which may facilitate mechanistic investigations in PID and its contribution to tubal factor infertility and ovarian carcinogenesis.
为了促进对盆腔炎性疾病(PID)及随后的输卵管因素不孕症以及卵巢癌发生机制的研究,我们试图建立源自患者组织的输卵管(FT)类器官,并研究它们对急性阴道细菌感染的炎症反应。实验研究。学术医学和研究中心。FT组织取自4例因良性妇科疾病行输卵管切除术的患者。我们通过向类器官培养基接种两种常见的阴道细菌物种 和 ,在FT类器官培养系统中引入急性感染。通过249个炎症基因的表达谱分析急性细菌感染后类器官引发的炎症反应。与未用任何细菌培养的阴性对照相比,用任一细菌物种培养的类器官均显示出多个差异表达的炎症基因。在 感染的类器官和 感染的类器官之间观察到明显差异。C-X-C基序趋化因子配体(CXCL)家族的基因在 感染的类器官中高度上调。流式细胞术显示免疫细胞在类器官培养过程中迅速消失,表明细菌培养观察到的炎症反应是由类器官中的上皮细胞产生的。结论:源自患者组织的FT类器官对急性细菌感染有反应,不同阴道细菌物种特异性的炎症基因上调。FT类器官是研究细菌感染期间宿主-病原体相互作用的有用模型系统,这可能有助于对PID及其对输卵管因素不孕症和卵巢癌发生的作用进行机制研究。
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