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Mechanistic insights into endometriosis: roles of Streptococcus agalactiae and L-carnitine in lesion development and angiogenesis

作者:Yuan Zhuang, Ting Lyu, Yang Chen, Xing Li, Lei Tang, Shiping Xian, Pengfei Yang, Lijie Wang, Qianqian Zhang, Chaoming Mei, Yu-jing Lin, Zhixiang Yan, Zhanyu Li, Jianzhong He, Fa‐Min Zeng · 发表于:Angiogenesis · 年份:2025 · DOI:10.1007/s10456-025-09991-7 · 被引用次数:4 · 研究领域:Endometriosis Research and Treatment、Reproductive System and Pregnancy、Endometrial and Cervical Cancer Treatments

Retrograde menstruation is a widely recognized etiological factor for endometriosis (EMs); however, it is not the sole cause, as not all affected women develop EMs. Emerging evidence suggests a significant association between the vaginal microbiota and EMs. Nonetheless, the precise mechanisms by which microbial communities influence the pathophysiology and progression of EMs remain unclear. In this study, the cervical mucus from patients with EMs showed significantly greater microbial abundance compared with that of controls, with Streptococcus agalactiae (S. agalactiae) exhibiting the most substantial increase as determined by 16S rRNA gene sequencing. In a murine model, elevated S. agalactiae levels significantly increased the lesion number and colonization, whereas antibiotic treatment reduced lesion formation. Metabolomic analyses showed elevated L-carnitine levels in the cervical secretions and serum of patients with EMs, a finding corroborated in murine tissues. Exogenous L-carnitine administration similarly increased the number and weight of endometriotic lesions. Meanwhile, the inhibition of L-carnitine synthesis suppressed lesion formation induced by S. agalactiae. In vitro, both S. agalactiae and L-carnitine promoted EMs cell proliferation, migration, and invasion. L-carnitine synthesis inhibition attenuated cell motility stimulated by S. agalactiae. Mechanistically, S. agalactiae enhanced angiogenesis through L-carnitine by upregulating vascular endothelial growth ...