Short-term exposure to a mixture of tributyltin plus cadmium disrupts the female reproductive organs, inducing ovarian follicular depletion and metabolic offspring outcomes in rats.

Tributyltin (TBT) and cadmium (Cd) are environmental pollutants that separately cause reproductive problems. However, the reproductive effects of exposure to a mixture of TBT plus Cd are not well known. We hypothesized that exposure to a mixture of TBT plus Cd (TBT + Cd) changes reproductive function. Female rats were treated with the TBT + Cd mixture daily for 15 days, after which tissue chemical deposition, histology, hormone levels, inflammation, collagen deposition, and protein expression in the ovary and uterus were assessed. Increased tin (Sn) and Cd levels were identified in the sera and livers of TBT + Cd rats. TBT + Cd rats displayed abnormal estrous cycles, reduced serum estrogen and testosterone levels, reduced ovarian reserve and antral follicles, corpora lutea, and total healthy follicle numbers compared to controls, suggesting ovarian follicular depletion. Uterine hypertrophy, inflammation and high collagen deposition were noted in TBT + Cd rats. TBT + Cd rats had increased ovarian and uterine mast cell numbers compared to controls, suggesting inflammation. An increase in estrogen receptor alpha (ERα) and progesterone receptor (PR) positive cells was noted in the ovaries and uteri of TBT + Cd rats. Prenatal TBT + Cd exposure altered serum glucose and triglyceride levels in the offspring, which may contribute to an unhealthy developmental environment. Collectively, these data indicate that TBT + Cd exposure changes female reproductive function, contributing to ovarian follicular depletion, uterine inflammation and fibrosis, and metabolic abnormalities in the prenatal exposure offspring.