The role of endocrine disrupting chemicals and weight in the onset of female puberty via epigenetic mechanisms

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Mammalian puberty is initiated by the pulsatile release of Gonadotropin-releasing hormone (GnRH) from a specialized group of neurons located in the hypothalamus. A network of inhibitory and stimulatory neurotransmitters, orchestrated by upstream transcriptional regulators, controls this process. Evidence has accumulated that timing and progression of puberty are affected by exogenous (endocrine disrupting chemicals, EDCs) and endogenous (weight/obesity) factors resulting in profound impairment of health not only in the first but additionally in further generations. The underlying mechanism is unknown. In this application we propose the highly innovative concept that epigenetic mechanisms, such as DNA methylation, chromatin modifications and members of Polycomb group silencers, might be targets for EDC and overweight subsequently affecting the expression of genes involved in the functional regulation of GnRH neurons and modifying the timing of pubertal onset in female rodents.