ESPE2022 Working Group Symposia ESPE Working Group on Paediatric and Adolescent Gynaecology (PAG) Symposium (4 abstracts)
To attain sexual competence, all mammalian species go through puberty, a maturational period during which body growth and development of secondary sexual characteristics occurs. Puberty begins with the reawakening of the gonadotropin-releasing hormone (GnRH) pulse generator. Reduction in inhibitory transsynaptic inputs combined with increased transsynaptic and glial excitatory inputs to the GnRH neuronal network are responsible for pubertal activation of GnRH neuro-secretion. During the infantile to juvenile transition, increased Arcuate Nucleus (ARC) Kiss1 expression is needed for activation of GnRH pulsatile secretion, since humans and animal models with mutations in the Kiss1 signaling pathway show pubertal failure and infertility. Although the pubertal process is known to have a strong genetic component, during the last several years, evidence has emerged suggesting that these genes are regulated by an epigenetic mechanism. Using the Kiss1 gene as a molecular readout of reproductive maturation, we demonstrated that the Polycomb group (PcG) of transcriptional repressors is in charge of epigenetically repressing ARC Kiss1 expression during the infantile period. Moreover, as animals approach the juvenile period, the Trithorax group (TrxG) of epigenetic activators counteract the PcG by imposing activating histone marks in the Kiss1 5’ regulatory regions, allowing for increased Kiss1 expression and thus puberty to progress. Furthermore, using a model of metabolic alteration of pubertal development we identified NAD-Dependent Protein Deacetylase Sirtuin-1 (SIRT1) as a relay of metabolic information in ARC Kiss1 neurons that controls Kiss1 expression by regulating the levels of histone acetylation and PcG binding in response of metabolic status. Here, we will briefly review the function of these epigenetic modifying enzymes and discuss the overall role of epigenetic markers in neuroendocrine reproductive development.
15 Sep 2022 - 17 Sep 2022