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孕期感染诱发的需氧菌性阴道炎可通过IL-4/JAK-1/STAT-6途径导致不良妊娠结局。

Aerobic Vaginitis Induced by Infection During Pregnancy Can Result in Adverse Pregnancy Outcomes Through the IL-4/JAK-1/STAT-6 Pathway.

作者信息

Fan Chong, Dai Youjin, Zhang Lei, Rui Can, Wang Xinyan, Luan Ting, Fan Yuru, Dong Zhiyong, Hou Wenwen, Li Ping, Liao Qinping, Zeng Xin

机构信息

Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Key Laboratory of Model Animal Research, Animal Core Facility of Nanjing Medical University, Nanjing Medical University, Nanjing, China.

出版信息

Front Microbiol. 2021 Apr 7;12:651426. doi: 10.3389/fmicb.2021.651426. eCollection 2021.

DOI:10.3389/fmicb.2021.651426
PMID:33897665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8058192/
Abstract

Aerobic vaginitis (AV) can occur if normal vaginal microflora are dominated by aerobic bacteria, seriously affects not only female health, but also fetal health while they are pregnant. Besides, pregnant status also aggravates the symptoms and consequences of the infection. Here, we infected pregnant BALB/c mice with on embryonic day 4.5 (E4.5) (study group), and administered an equivalent volume of phosphate-buffered saline in another cohort of pregnant mice (control group). We recorded the weight of pregnant mice and their fetuses. The maternal and fetal weight of the study group decreased in comparison with that of the control group, whereas the weight of placenta increased in the study group. Then, five genes with significant upregulation and 15 genes with downregulation were screened. Expression of interleukin 4 (IL-4) mRNA in the study group decreased to 18.5%. Enzyme-linked immunosorbent assay results showed IL-4 expression in mouse plasma declined in the study group at E11.5 and E18.5. mRNA expression of chemokine (c-c motif) ligand (CCL)-17, CCL-22, CCL-24, IL-4, Janus Kinase (JAK)-1, signal transducer and activator of transcription (STAT)-6, and GATA-3 showed significant downregulation in placental and uterine tissues. Flow cytometry of primary decidual macrophages (DMs) revealed more M1-like macrophages in the study group. And after addition of IL-4 to DMs, more M1 macrophages polarized to M2 type macrophages. We did not discover bacteria existed in mouse placentas. Our study affords a feasible method for exploring and managing AV during pregnancy.

摘要

如果正常阴道微生物群以需氧菌为主，就可能发生需氧菌性阴道炎（AV），这不仅会严重影响女性健康，还会在女性怀孕期间影响胎儿健康。此外，怀孕状态也会加重感染的症状和后果。在此，我们在胚胎第4.5天（E4.5）感染怀孕的BALB/c小鼠（研究组），并在另一组怀孕小鼠中给予等量的磷酸盐缓冲盐水（对照组）。我们记录了怀孕小鼠及其胎儿的体重。与对照组相比，研究组的母鼠和胎儿体重下降，而研究组的胎盘重量增加。然后，筛选出5个显著上调的基因和15个下调的基因。研究组中白细胞介素4（IL-4）mRNA的表达降至18.5%。酶联免疫吸附测定结果显示，在E11.5和E18.5时，研究组小鼠血浆中IL-4的表达下降。趋化因子（c-c基序）配体（CCL）-17、CCL-22、CCL-24、IL-4、Janus激酶（JAK）-1、信号转导子和转录激活子（STAT）-6以及GATA-3的mRNA表达在胎盘和子宫组织中显著下调。原代蜕膜巨噬细胞（DMs）的流式细胞术显示，研究组中有更多的M1样巨噬细胞。并且在向DMs中添加IL-4后，更多的M1巨噬细胞极化为M2型巨噬细胞。我们未在小鼠胎盘中发现细菌存在。我们的研究为探索和管理孕期需氧菌性阴道炎提供了一种可行的方法。

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