Akshitha Sahu
Research Mentor(s): Soundara Viveka Thangaraj
Mentor Department: Pediatrics
Authors: Akshitha Sahu, Vasantha Padmanabhan, Soundara Viveka Thangaraj
Session: Session 3 (11:00am – 11:50am)
Presentation Type: Poster 115
Abstract
We are chronically exposed to several different environmental chemicals (EC) at low doses, which potentially contributes to the increasing noncommunicable disease burden. Existing studies using single chemicals have shown that prenatal exposure to these chemicals leads to adverse effects on metabolic health. However, these do not reflect the real world conditions of chronic exposure to low doses of a mixture of ECs. Hence, we used sheep exposed to biosolids, a derivative of human wastewater treatment containing more than 700 ECs, as a real-life exposure model. Prior studies examining prenatal exposure to biosolids have found metabolic perturbations, such as heavier thyroid glands in male fetuses and reduced prepubertal body weight followed by catchup growth in male offspring. We hypothesize that prenatal exposure to a low-dose EC mixture leads to sexually dimorphic effects on lipid metabolism in lambs. Pregnant ewes (F0) were raised on pastures treated with inorganic fertilizer (Control) or biosolids (BTP) throughout gestation. The F1 lambs (n = 15/group with male n = 7/group and females n = 8/group) were raised on Control pastures from birth until they were euthanized at 9.5 weeks. Hepatic lipid accumulation in the lambs was evaluated using Oil Red O staining on liver cryosections and measuring triglyceride concentration in the plasma and liver tissue with a colorimetric assay kit (Cayman chemicals). BTP male lambs showed significantly elevated plasma triglyceride concentration (1.63-fold increase, P = 0.04) and a trend toward increased liver triglyceride concentrations by two-way ANOVA. No significant liver lipid accumulation was observed. These findings suggest an altered lipid metabolic mechanism in response to prenatal EC exposure, with elevated plasma triglycerides potentially predisposing these lambs to adverse metabolic health outcomes later in life. Further exploration of metabolism in the adult offspring is needed to understand the long-term implications of these alterations. This study in the precocial sheep model with a developmental trajectory similar to humans is of translational relevance.
