Toffoli Miriam, Campisciano Giuseppina, Santin Aurora, Pegoraro Silvia, Zito Gabriella, Spedicati Beatrice, Balduit Andrea, Romano Federico, Di Lorenzo Giovanni, Mangogna Alessandro, Tesolin Paola, Nardone Giuseppe Giovanni, Zanotta Nunzia, Sanna Serena, Crobu Francesca, Kishore Uday, Ricci Giuseppe, Bulla Roberta, Girotto Giorgia, Agostinis Chiara
Department of Medical, Surgical and Health Science, University of Trieste, Trieste, Italy.
Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy.
Life Sci. 2025 Mar 1;364:123427. doi: 10.1016/j.lfs.2025.123427. Epub 2025 Jan 30.
Endometriosis (EM) is a chronic inflammatory disorder with multifactorial etiologies (i.e., genetics and environmental factors, hormonal and immunological changes, and microbiome alterations). The complement system is one of the most frequently dysregulated pathways in EM. Mannose-binding lectin (MBL), a carbohydrate pattern recognition molecule, is the first described recognition subcomponent of the complement lectin pathway (LP). Here, we unveiled the interplay among MBL polymorphisms, plasma levels, LP functionality, and microbiota as potential contributors to EM pathogenesis.
A cohort of 38 EM patients and 20 healthy controls was enrolled, and the levels and functionality of the LP were assessed via ELISA. MBL genetic variants and the endometrial and vaginal microbiome were investigated and correlated.
High MBL levels were related to the disease severity, although not accountable for the MBL2 genotype. MBL and MASP-2 were present in the uterine mucosa but appeared to have no activity at the endometriotic lesion. EM patients with LP functional deficit displayed pathogenic bacterial species more frequently in the endometrial microbiome. Moreover, women affected by EM showed a higher frequency of rare gene variants in the estrogen pathway genes, potentially affecting MBL plasma levels.
A lower functionality of LP in the uterine mucosa may contribute to an unbalanced bacterial environment that could activate endometrial cells. Not only the genotype and the inflammatory condition, but also the estrogen pathway can cause altered MBL levels, thus contributing to changes in the LP functionality.
子宫内膜异位症（EM）是一种病因多因素的慢性炎症性疾病（即遗传和环境因素、激素和免疫变化以及微生物群改变）。补体系统是EM中最常失调的途径之一。甘露糖结合凝集素（MBL）是一种碳水化合物模式识别分子，是补体凝集素途径（LP）中最早被描述的识别亚成分。在此，我们揭示了MBL多态性、血浆水平、LP功能和微生物群之间的相互作用，它们可能是EM发病机制的潜在因素。
招募了38名EM患者和20名健康对照者，通过ELISA评估LP的水平和功能。研究了MBL基因变异以及子宫内膜和阴道微生物群，并进行相关性分析。
高MBL水平与疾病严重程度相关，尽管与MBL2基因型无关。MBL和MASP-2存在于子宫黏膜中，但在子宫内膜异位病变处似乎没有活性。LP功能缺陷的EM患者在内膜微生物群中更频繁地出现致病细菌种类。此外，受EM影响的女性在雌激素途径基因中出现罕见基因变异的频率更高，这可能会影响MBL血浆水平。
子宫黏膜中LP功能降低可能导致细菌环境失衡，从而激活子宫内膜细胞。不仅基因型和炎症状态，雌激素途径也会导致MBL水平改变，进而导致LP功能变化。
