Developmental Programming: Sex-specific Effects of Prenatal Exposure to a Real-Life Mixture of Environmental Chemicals on Liver Function and Transcriptome in Sheep.

ABSTRACT: Humans are chronically exposed to a mixture of environmental chemicals (ECs), many with endocrine disrupting potential, contributing to the development of non-communicable diseases. The adverse health effects of exposure to single ECs have been extensively studied but less is known about the impact of chronic exposure to low levels of a mixture of ECs, which is the real-life exposure scenario. Biosolids, derived from human wastewater treatment, closely reflects the human exposome in both the array and concentration of ECs and is a novel, real-life model to investigate the health risks posed by developmental exposure to mixtures of ECs. Previous studies using the prenatal biosolids exposure model found an increased accumulation of the endocrine disrupting chemical diethylhexylphthalate in the fetal liver and metabolic perturbations including increased thyroid gland weight in the male fetus and reduced bodyweight in prepubertal male lambs. To understand the basis of this sexually dimorphic metabolic phenotype we investigated the transcriptome of liver, the primary metabolic organ, in lambs of both sexes. Since many liver genes show sexual dimorphism, with sex-biased genes playing a pivotal role in lipid and drug metabolism, sex-differences in liver gene expression and the impact of prenatal biosolids exposure on it was examined. We hypothesized that maternal preconceptional and gestational exposure of sheep to biosolids programs sex-specific transcriptional changes in the offspring liver. Ewes (F0) were grazed on either inorganic fertilizer (Control) or biosolids-treated pastures (Biosolids) from 1 month before mating till parturition. All lambs (F1) were raised on control pastures after lambing until euthanasia at 9.5 weeks of age. RNA from liver from Control male (n=7), Control female (n=8), BTP male (n=7) and BTP female (n=8) lambs were subjected to next generation sequencing and DESeq2 R package was used to identify differentially expressed genes due to prenatal biosolids exposure and sex-differentially expressed genes .

ORGANISM(S): Ovis aries

PROVIDER: GSE270391 | GEO | 2025/01/12

REPOSITORIES: GEO