Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is widely used to enhance the flexibility and durability of various products. As an endocrine disruptor, DEHP can interfere with normal hormonal functions, posing substantial health risks to organisms. Given the critical role of the liver in DEHP metabolism, we investigated potential liver damage in offspring induced by prenatal exposure to low doses of DEHP in Sprague Dawley rats. Pregnant rats were divided into three groups and administered 20 or 200 μg/kg/day of DEHP or corn oil vehicle control via oral gavage from gestation days 0-20. Male rat offspring were euthanized on postnatal day 84, and blood and liver specimens were collected for analysis. We observed fibrotic changes in the livers of the exposed groups, accompanied by the proliferation and activation of hepatic stellate cells and upregulated expression of TGF-B and collagen 1A1. Additionally, an inflammatory response, characterized by increased macrophage infiltration and elevated levels of pro-inflammatory cytokines, was evident. Third, hepatic and serum triglyceride and serum cholesterol were notably increased, along with upregulated expression of lipid metabolism-related proteins, such as sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, fatty acid synthase, and diacylglycerol O-acyltransferase 1, particularly in the low-dose group. These results suggest that prenatal exposure to DEHP can disrupt lipid metabolism, resulting in hepatic lipid accumulation in the offspring. This exposure may also induce an inflammatory response that contributes to the development of liver fibrosis. Thus, even at relatively low doses, such exposure can precipitate latent liver damage in offspring.
Keyphrases
- inflammatory response
- low dose
- fatty acid
- high fat diet
- binding protein
- pregnant women
- oxidative stress
- liver fibrosis
- poor prognosis
- preterm infants
- lipopolysaccharide induced
- high dose
- induced apoptosis
- adipose tissue
- systemic sclerosis
- signaling pathway
- insulin resistance
- type diabetes
- idiopathic pulmonary fibrosis
- lps induced
- risk assessment
- escherichia coli
- transcription factor
- mass spectrometry
- skeletal muscle
- long non coding rna
- anti inflammatory
- cell proliferation
- cell death
- cystic fibrosis
- staphylococcus aureus
- climate change
- cell cycle arrest
- endoplasmic reticulum stress
- fine needle aspiration
- pi k akt
- single molecule