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Introduction:Arteriovenous fistula (AVF) maturation and patency rates are decreased in women as a result of poorly defined processes. To illustrate the sexual diversities among female and male fistulas and to unveil potential mechanism we created a clinically relevant murine AVF model.Hypothesis:Sexual disparity between female and male murine AVFs is not due to inherent vascular morphometric differences but linked to distinct vascular remodeling patterns after AVF creation.Methods:Four weeks after partial nephrectomy surgery 18 female and 19 male C57BL/6J wild type (WT) mice underwent native AVF (n-AVF) surgeries by anastomosis end-jugular vein to side-contralateral-carotid artery. Another 26 transplanted AVF (t-AVF) surgeries were established by embedding donor inferior vena cava (IVC) from WT or global GFP mice into gender matched recipient GFP or WT n-AVF. Native graft vein (NGV) and transplanted graft vein (TGV) were collected for gene expression and histopathological assay. AVF patency and hemodynamic parameters were monitored by noninvasive Doppler detection weekly.Results:Female NGVs had significantly decreased peak velocity (PV), lumen vessel area, neointimal area and neointimal cell density than males. There were significant increases in TGF?1 (p<0.0001) and TGF? receptor1 (p<0.0001) gene expression as well as significant increasing in ?-SMA (p<0.05), FSP-1 (p<0.05), Collagen I (p<0.05) and pSMAD3 (p<0.05) protein expression in female NGVs. In female t-AVFs at day 14, reduced PV was due to remodeling of the vessel wall from circulating cells (from inside to outside). In contrast, in t-AVFs of male mice 14 days after t-AVF creation, neointimal lesions showed cellular accumulation originating from resident tissue cells (remodeling from outside to inside).Conclusions:Decreased AVF performance in female mice compared to male mice was not due to inherent diameter and hemodynamic parameters but rather an increase in TGF?1 signaling, fibrosis and infiltration of the fistula wall by circulating cells. These results provide valuable insights into the mechanisms of female detrimental outcomes which are linked to distinct vascular remodeling patterns occurring as early as 2 weeks after AVF creation.