Bisphenol A alters JUN promoter methylation, impairing steroid metabolism in placental cells and linking to sub-representative phenotypes
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Prenatal exposure to Bisphenol A (BPA) disrupts placental steroid metabolism by epigenetically downregulating the JUN gene. This leads to reduced hormone levels and shorter anogenital distance (AGD) in male offspring.
Area Of Science
- Endocrinology
- Epigenetics
- Toxicology
Background
- Bisphenol A (BPA) is an industrial chemical with endocrine-disrupting properties.
- Prenatal BPA exposure impacts placental function and steroid metabolism.
- Epigenetic mechanisms are implicated in BPA's effects on steroidogenesis.
Purpose Of The Study
- To investigate the epigenetic regulation of steroid metabolism by BPA in the placenta.
- To identify specific genes and pathways affected by BPA exposure.
- To correlate epigenetic changes with offspring phenotypes.
Main Methods
- JEG3 cells were treated with BPA to analyze hormone levels, DNA methylation, and gene expression.
- Gene promoter methylation and expression were validated in placental samples.
- Enrichment analysis identified key signaling pathways, including MAPK.
- Anogenital distance (AGD) was assessed in relation to JUN promoter methylation in offspring.
Main Results
- BPA significantly reduced progesterone, estradiol, and testosterone levels.
- BPA altered promoter methylation and expression of 63 genes, notably JUN.
- JUN promoter methylation inversely regulated its expression, impacting hormone levels.
- Male offspring with hypermethylated JUN promoters had shorter AGD.
Conclusions
- BPA reduces steroid metabolism gene expression through epigenetic regulation of the JUN gene.
- This epigenetic disruption leads to decreased sex hormone levels.
- BPA-induced epigenetic changes in JUN are associated with adverse offspring phenotypes like shortened AGD.
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
Related Concept Videos
The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
The gonads, namely the testes in males and the ovaries in females, are pivotal in producing gonadal hormones that orchestrate the intricate processes of sexual development and reproduction.
In males, testosterone is the primary gonadal androgen. It plays a central role in the maturation of male reproductive organs — the penis and testes. Additionally, testosterone is instrumental in the development of secondary sexual characteristics — a deep voice as well as facial and pubic hair...
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
In most mammals, females have two X chromosomes (XX) while males have an X and a Y chromosome (XY). The X chromosome contains significantly more genes than the Y chromosome. Therefore, to prevent an excess of X chromosome-linked gene expression in females, one of the two X chromosomes is randomly silenced during early development....
A drug's physicochemical properties fundamentally influence its metabolism. For instance, a drug's molecular size and shape critically determine its interaction with enzymes and transporters — larger drugs may face difficulty reaching enzyme active sites, altering their metabolic pathways. The pKa of a drug, which establishes its ionization state, can impact its solubility and absorption, thereby influencing metabolism.
The drug's acidity or basicity is essential in...