A single-cell and spatial transcriptomics study of the mouse female reproductive tract (FRT) reveals how estrous cycling, pregnancy, and aging shape the organs. The FRT undergoes extensive remodeling during the estrous cycle, with fibroblasts playing a central, highly organ-specific role in orchestrating extracellular matrix (ECM) reorganization and inflammation. The study shows that fibroblasts regulate inflammation and ECM remodeling, and that incomplete resolution of cyclic remodeling leads to fibrosis and chronic inflammation. The results suggest a model where recurrent FRT remodeling over a reproductive lifespan drives age-related fibrosis and inflammation. This hypothesis was tested by chemical ablation of cycling, which reduced fibrotic accumulation during aging. The study provides an atlas of the FRT, revealing how estrus, pregnancy, and aging shape the organs and the unexpected cost of the recurrent remodeling required for reproduction. The FRT organs show distinct compositional and transcriptional differences, with the upper tract (ovary, oviduct, uterus) and lower tract (cervix, vagina) showing different immune and ECM dynamics. The study also shows that fibroblast functions are dynamically regulated throughout the cycle but not coordinated between organs. The results highlight the organ-specific impact of fibroblast chronic inflammation during FRT aging and the accumulation of fibrosis with age in the oviduct, uterus, and vagina. The study also shows that cycling directly contributes to fibrosis, with the age-related collagen accumulation rate best predicted by the maximum phase-specific ECM activity in the cycle. The findings suggest that both aging and cycling independently contribute to fibrosis development through incompletely resolved ECM remodeling. The study provides insights into the molecular mechanisms underlying the relationship between reproductive cycles and fibrosis, and highlights the importance of understanding the FRT in the context of aging and disease.A single-cell and spatial transcriptomics study of the mouse female reproductive tract (FRT) reveals how estrous cycling, pregnancy, and aging shape the organs. The FRT undergoes extensive remodeling during the estrous cycle, with fibroblasts playing a central, highly organ-specific role in orchestrating extracellular matrix (ECM) reorganization and inflammation. The study shows that fibroblasts regulate inflammation and ECM remodeling, and that incomplete resolution of cyclic remodeling leads to fibrosis and chronic inflammation. The results suggest a model where recurrent FRT remodeling over a reproductive lifespan drives age-related fibrosis and inflammation. This hypothesis was tested by chemical ablation of cycling, which reduced fibrotic accumulation during aging. The study provides an atlas of the FRT, revealing how estrus, pregnancy, and aging shape the organs and the unexpected cost of the recurrent remodeling required for reproduction. The FRT organs show distinct compositional and transcriptional differences, with the upper tract (ovary, oviduct, uterus) and lower tract (cervix, vagina) showing different immune and ECM dynamics. The study also shows that fibroblast functions are dynamically regulated throughout the cycle but not coordinated between organs. The results highlight the organ-specific impact of fibroblast chronic inflammation during FRT aging and the accumulation of fibrosis with age in the oviduct, uterus, and vagina. The study also shows that cycling directly contributes to fibrosis, with the age-related collagen accumulation rate best predicted by the maximum phase-specific ECM activity in the cycle. The findings suggest that both aging and cycling independently contribute to fibrosis development through incompletely resolved ECM remodeling. The study provides insights into the molecular mechanisms underlying the relationship between reproductive cycles and fibrosis, and highlights the importance of understanding the FRT in the context of aging and disease.