Maternal Di-(2-ethylhexyl)-Phthalate exposure during pregnancy altered energy metabolism in immature offspring and caused hyperglycemia

• Published in: Ecotoxicology and environmental safety Vol. 279; p. 116494
• Main Authors: Huang, Binbin, Zhang, Na, Wang, Juan, Gao, Yue, Wu, Wanxin, Jiang, Minmin, Han, Maozhen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-07-2024; Elsevier
• Subjects: Di-(2-ethylhexyl)-Phthalate (DEHP); Gut microbiota; Liver; Placenta; Transcriptome; Gut microbiota; Di-(2-ethylhexyl)-Phthalate (DEHP); Placenta; Liver; Transcriptome
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.116494

Di-(2-ethylhexyl)-phthalate (DEHP), as distinctive endocrine disrupting chemicals, has become a global environmental pollutant harmful to human and animal health. However, the impacts on offspring and mothers with maternal DEHP exposure are largely unknown and the mechanism remains elusive. We established DEHP-exposed maternal mice to investigate the impacts on mother and offspring and illustrate the mechanism from multiple perspectives. Pregnant mice were administered with different doses of DEHP, respectively. Metagenomic sequencing used fecal and transcriptome sequencing using placentas and livers from offspring have been performed, respectively. The results of the histopathology perspective demonstrated that DEHP exposure could disrupt the function of islets impact placentas and fetus development for maternal mice, and cause the disorder of glucose and lipid metabolism for immature offspring mice, resulting in hyperglycemia. The results of the metagenome of gut microbial communities indicated that the dysbiosis of gut microbiota in mother and offspring mice and the dominant phyla transformed through vertical transmission. Transcriptome analysis found DEHP exposure induced mutations of Ahcy and Gstp3, which can damage liver cells and affect the metabolism of the host. DEHP exposure harms pregnant mice and offspring by affecting gene expression and altering metabolism. Our results suggested that exposure of pregnant mice to DEHP during pregnancy and lactation increased the risk of metabolic disorders by altering key genes in liver and gut microbiota, and these results provided new insights into the potential long-term harms of DEHP.
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•Maternal DEHP exposure disturbed glucose and lipid metabolism of both mother and offspring mice, which caused offspring mice suffered from hyperglycemia.•Maternal DEHP exposure contribute to gene expression of placenta and liver tissues in mother and offspring mice, respectively.•Maternal DEHP exposure alters the composition of gut microbiota in both mother and offspring mice.•Multi-omics analysis revealed that the mechanism of maternal DEHP exposure disrupted offspring energy metabolism through placenta-liver and the vertical transmission of the gut microbiota.