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Aims: 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., Materials and Methods: 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., Key Findings: 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., Significance: 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., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

FOXL2 belongs to the evolutionarily conserved forkhead box (FOX) superfamily and is a master transcription factor in a spectrum of developmental pathways, including ovarian and eyelid development and bone, cartilage and uterine maturation. To analyse its action, we searched for proteins that interact with FOXL2. We found that FOXL2 interacts with specific C-terminal propeptides of several fibrillary collagens. Because these propeptides can participate in feedback regulation of collagen biosynthesis, we inferred that FOXL2 could thereby affect the transcription of the cognate collagen genes. Focusing on COL1A2, we found that FOXL2 indeed affects collagen synthesis, by binding to a DNA response element located about 65Kb upstream of this gene. According to our hypothesis we found that in Foxl2(-/-) mouse ovaries, Col1a2 was elevated from birth to adulthood. The extracellular matrix (ECM) compartmentalizes the ovary during folliculogenesis, (with type I, type III and type IV collagens as primary components), and ECM composition changes during the reproductive lifespan. In Foxl2(-/-) mouse ovaries, in addition to up-regulation of Col1a2, Col3a1, Col4a1 and fibronectin were also upregulated, while laminin expression was reduced. Thus, by regulating levels of extracellular matrix components, FOXL2 may contribute to both ovarian histogenesis and the fibrosis attendant on depletion of the follicle reserve during reproductive aging and menopause., (Copyright © 2016 Elsevier Inc. All rights reserved.)