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Sustained UPR activation not only promotes the production of inflammatory mediators as previously described, multiple studies have also reported its association with cellular senescence ( 5.2 Microenvironmental disruption 5.2.1 Immune microenvironment alterations OS induced by obesity damages endometrial immune microenvironment and immune tolerance ( 5.2.2 Sexual hormone level disruption Under normal conditions, estrogen(E 2 ) undergoes two successive phases of metabolism: cytochrome P450 enzymes (such as CYP1A1) first metabolize E 2 into reactive metabolites (2-hydroxyestrogens and 4-hydroxyestrogens), which are then conjugated by sulfotransferase (SULT1E1) and UDP-glucuronosyltransferase (UGT2B7) to add a sulfonate (SO 3 - ) group and a glucuronide group, respectively ( 2 metabolism that convert reactive E 2 metabolites into their respective conjugates, which are water-soluble metabolites that are easily excreted