Mono-(2-ethyl-5-hydroxyhexyl) phthalate promotes uterine leiomyoma cell survival through tryptophan-kynurenine-AHR pathway activation

Uterine leiomyomas (or fibroids) represent the most common tumor affecting up to 80% of reproductive-age women. Epidemiological studies consistently indicate a positive association between exposure to endocrine-disrupting phthalates and leiomyoma risk; however, the underlying mechanisms remain unclear. Here, we demonstrate that the ubiquitous environmental pollutant mono-(2-ethyl-5-hydroxyhexyl) phthalate [MEHHP, the major metabolite of di-(2-ethylhexyl) phthalate] promotes leiomyoma cell survival through increasing cellular tryptophan uptake, kynurenine production, and aryl hydrocarbon receptor pathway activation. Both epidemiologically and mechanistically, our study identified MEHHP exposure as a high-risk factor for leiomyoma growth. These findings are expected to open new avenues in the leiomyoma research field and facilitate the development of novel intervention strategies for the treatment or prevention of the disease.