Phthalates are synthetic chemicals widely used as
plasticizers and stabilizers in various consumer products. Because of the extensive production and use of phthalates, humans are exposed to these chemicals daily. While most studies focus on a single
phthalate, humans are exposed to a mixture of phthalates on a regular basis. The impact of continuous exposure to
phthalate mixture on uterus is largely unknown. Thus, we conducted studies in which adult female mice were exposed for 6 months to 0.15 ppm and 1.5 ppm of a mixture of phthalates via chow ad libitum. Our studies revealed that consumption of
phthalate mixture at 0.15 ppm and 1.5 ppm for 6 months led to a significant increase in the thickness of the myometrial layer compared to control. Further investigation employing
RNA-sequencing revealed an elevated
transforming growth factor beta (TGF-β) signaling in the uteri of mice fed with
phthalate mixture. TGF-β signaling is associated with the development of
fibrosis, a consequence of excessive accumulation of extracellular matrix components, such as
collagen fibers in a tissue. Consistent with this observation, we found a higher incidence of
collagen deposition in uteri of mice exposed to
phthalate mixture compared to unexposed controls. Second Harmonic Generation (SHG) imaging showed disorganized
collagen fibers and nanoindentation indicated a local increase in uterine stiffness upon exposure to
phthalate mixture. Collectively, our results demonstrate that chronic exposure to
phthalate mixture can have adverse effects on uterine homeostasis.