Disruption of fertility, placenta, pregnancy outcome, and multigenerational inheritance of hepatic steatosis by organotin exposure from contaminated seafood in rats

摘要

Early life exposure to endocrine-disrupting chemicals (EDCs) is an emerging risk factor for development of complications later in life and in subsequent generations. We previously demonstrated that exposure to the EDC organotin (OT), which is present in contaminated seafood, resulted in reproductive abnormalities in female rats. However, few studies have explored the effect of OT accumulation in seafood on pregnancy outcomes. This led us to consider the potential effects of the OT present in seafood on fertility, pregnancy, the placenta, and the offspring. In this investigation, we assessed whether exposure to the OT in contaminated seafood resulted in abnormal fertility and pregnancy features and offspring complications. OT in contaminated seafood (LNI) was administered to female rats, and their fertility, pregnancy outcomes, and fetal liver morphology were assessed. LNI caused abnormal fertility, a reduction in the total number of pups, and an increase in serum testosterone levels compared to controls. Furthermore, LNI exposure caused irregular uterine morphology with inflammation and fibrosis and led to a reduction in embryonic implantation. In pregnant rats, LNI caused abnormal lipid profiles and livers with steatosis features. LNI exposure also causes placental morpho-physiology disruption, a high presence of glycogen and inflammatory cells, and irregular lipid profiles. In addition, LNI exposure caused an increase in large amounts of carbohydrate and lipid delivery to the fetus via an increase in placental nutrient sensor protein expressions (GLUT1, IRβ/mTOR and Akt). In both genders of offspring, LNI exposure led to an increase in body weights, liver megakaryocytes, lipid accumulation, and oxidative stress (OS) levels. Collectively, these data suggest that OT exposure from contaminated seafood in female rats leads to reduced fertility, uterine implantation failure, pregnancy and placental metabolic outcome irregularities, offspring adiposity, liver steatosis, and an increase in OS. Furthermore, some of the effects of OT may be the result of obesogenic and multigenera-tional effects of OT in adult female rats.