Zhao Xingping, Zhao Qun, Zhu Xiuting, Huang Huan, Wan Xing, Guo Rui, Zhao Yanqiu, Chen Dan, Xu Dabao
Department of Gynecology, Third Xiangya Hospital of Central South University, Changsha 410013, China.
Scientific Research Centre, The Third Hospital Affiliated to the Chinese University of Hong Kong, Shenzhen 518172, China.
Ann Transl Med. 2020 Feb;8(4):52. doi: 10.21037/atm.2019.11.124.
Intrauterine adhesion (IUA) is one of the most important causes of female infertility, while iatrogenic endometrial injury is the main, but not the entire, cause of IUA. The microorganisms of the female reproductive tract play an important role in its health and disease. The imbalance of immune regulation caused by the imbalance of reproductive tract dysbacteriosis may be an important link in the formation mechanism of uterine cavity adhesion.
We prospectively enrolled 30 patients diagnosed with IUA and 30 women with a history of intrauterine surgery, but without IUA, as control subjects. All participants were diagnosed with hysteroscopy while two swabs-one being leucorrhea drawn from the middle of the vagina and the other being cervical mucus drawn from the cervical canal-were taken. The bacterial load and community were identified by 16S rDNA quantitative polymerase chain reaction and pyrosequencing. Immunocytokines in serum were quantitatively detected by human T-helper cytokine kit. The correlation between Th cytokines and microorganisms in IUA and non-IUA groups was analyzed.
Compared with non-IUA participants at the phylum level, patients with IUA had a significantly higher percentage of firmicutes in most samples, while the diversity of bacteria was significantly decreased. Some species that were members of vaginal and cervical canal bacterial phyla, including Euryarchaeota, Acidobacteria, Chlamydiae, Chlorobi, Planctomycetes and TM6 (Dependentiae), almost disappeared. The quantity in serum of IUA patients of classical proinflammatory cytokines IL-6 and TNF-γ, released from immune cells, also known as profibrotic cytokines, were significantly higher than that of the non-IUA women in our study (P<0.05).
IUA is characterized by an increased bacterial burden, decreased diversity of bacterial communities in the vagina/cervical canal, and increased immune cytokines of pro-fibrosis, which may predict new and more effective therapeutic schemes for the treatment of IUA.
宫腔粘连(IUA)是女性不孕的重要原因之一,而医源性子宫内膜损伤是IUA的主要但非唯一原因。女性生殖道微生物在其健康和疾病中起重要作用。生殖道菌群失调导致的免疫调节失衡可能是宫腔粘连形成机制中的重要环节。
我们前瞻性纳入了30例诊断为IUA的患者和30例有宫腔手术史但无IUA的女性作为对照。所有参与者均接受宫腔镜检查,并采集两份拭子——一份是从阴道中部采集的白带,另一份是从宫颈管采集的宫颈黏液。通过16S rDNA定量聚合酶链反应和焦磷酸测序鉴定细菌载量和群落。用人辅助性T细胞细胞因子试剂盒定量检测血清中的免疫细胞因子。分析IUA组和非IUA组中Th细胞因子与微生物之间的相关性。
在门水平上,与非IUA参与者相比,IUA患者在大多数样本中的厚壁菌门百分比显著更高,而细菌多样性显著降低。一些属于阴道和宫颈管细菌门的物种,包括广古菌门、酸杆菌门、衣原体门、绿菌门、浮霉菌门和TM6(依赖菌门)几乎消失。在我们的研究中,IUA患者血清中由免疫细胞释放的经典促炎细胞因子IL-6和TNF-γ(也称为促纤维化细胞因子)的量显著高于非IUA女性(P<0.05)。
IUA的特征是细菌负荷增加、阴道/宫颈管细菌群落多样性降低以及促纤维化免疫细胞因子增加,这可能为IUA的治疗预测新的、更有效的治疗方案。