RESUMO
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, IRß/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 multigenerational effects of OT in adult female rats.
Assuntos
Fígado Gorduroso , Compostos Orgânicos de Estanho , Animais , Feminino , Fertilidade , Masculino , Placenta , Gravidez , Resultado da Gravidez , RatosRESUMO
Organotins (OTs) are environmental contaminants used as biocides in antifouling paints that have been shown to be endocrine disrupters. However, studies evaluating the effects of OTs accumulated in seafood (LNI) on reproductive health are particularly sparse. This study demonstrates that LNI leads to impairment in the reproductive tract of female rats, as the estrous cycle development, as well as for ovary and uterus morphology. Rats were treated with LNI, and their reproductive morphophysiology was assessed. Morphophysiological abnormalities, such as irregular estrous cycles, abnormal ovarian follicular development and ovarian collagen deposition, were observed in LNI rats. An increase in luminal epithelia and ERα expression was observed in the LNI uteri. Together, these data provide in vivo evidence that LNI are toxic for reproductive morphophysiology, which may be associated with risks to reproductive function.