Nuclear receptors in transgenerational epigenetic inheritance

Area of Science:

• Endocrinology
• Genetics
• Toxicology

Background:

• Nuclear receptors are transcription factors linking lipid environment to genetic programs.
• They are key mediators in rapid species adaptation and fine-tuning physiological processes.
• Small molecules like hormones and xenobiotics can modulate nuclear receptor activity.

Purpose of the Study:

• To review the role of nuclear receptors in transgenerational inheritance.
• To explore how small molecules and environmental factors influence transgenerational changes via nuclear receptors.
• To summarize current knowledge on nuclear receptor-mediated transgenerational effects.

Main Methods:

• Literature review of studies on nuclear receptors and transgenerational inheritance.
• Analysis of molecular mechanisms linking environmental exposures to nuclear receptor activation.
• Examination of studies on environmental stress and maternal behavior effects on nuclear receptor expression.

Main Results:

• Environmental chemicals (phthalates, BPA, nicotine, tributylin) activate nuclear receptors (ERs, AR, GR, PPARγ), inducing transgenerational changes.
• Environmental stress and maternal behavior can alter Estrogen and glucocorticoid receptor expression in the second generation.
• These alterations initiate modified genetic programs in subsequent generations.

Conclusions:

• Nuclear receptors are critical mediators of transgenerational inheritance.
• Both direct ligand activation and indirect epigenetic modifications involving nuclear receptors contribute to transgenerational traits.
• Understanding these pathways is crucial for assessing environmental impacts on inheritance.