The effect of N-butyl benzyl phthalate, a common plasticizer, on endometriosis development

Abstract Endometriosis is an estrogen-dependent and chronic inflammatory disease, which retrograded menstrual endometrial cells enter the pelvis and abnormally grow outside the uterine cavity. Severe symptoms such as infertility and chronic pelvic pain are typically observed in 6%–10% of reproductive-aged women. Previous study demonstrates that phthalates are capable to disrupt the endocrine system, especially by mimicking estrogen functions. Among them, n-butyl benzyl phthalate (BBP), a plasticizer for vinyl foams and artificial leather, is able to work as a selective agonist through the binding of ERα, and subsequently interrupt the endocrine regulation. This study aimed to explore the effect of BBP on endometriosis. We established a surgery-induced murine model and exposed the mice at physiologically relevant dose of BBP mimicking human exposure. The result showed that chronic exposure to BBP did not promote the growth of endometrial lesions, however, the lesion survival rate in BBP-treated mice was significantly increased compared to vehicle-treated mice. Our data showed that BBP exposure promoted the infiltration of monocytes (Ly6c+CD11b+F4/80-) and plasmacytoid dendritic cells (pDCs; CD11c+/lowPDCA-1+) in the lesions. In addition, the percentages of CD44+ cells in the infiltrated monocytes and pDCs in the BBP-treated group were significantly higher than those in the control. Also, BBP exposure promoted ICAM-1 expression in CD45− endometriotic lesion cells. The results suggest that BBP exposure may enhance endometrial cell adhesion through altering innate cell subset migration. The detail mechanism of BBP effect on endometriosis development awaits further investigation.