INDUCTION OF EPIGENETIC MODIFICATIONS BY ENDOCRINE-DISRUPTING CHEMICALS

JORGELINA VARAYOUD; FLORENCIA DONÁ; MARIA EMILIA RACCA; AILÍN ALMIRÓN; MARÍA PAULA GASTIAZORO; MILENA DURANDO; VIRGINIA LORENZ; MARÍA MERCEDES MILESI

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias.; 2023

SAIC, SAB, AAFE y AACYTAL

Endocrine-disrupting chemicals (EDCs) are widespread due to their numerous and frequent use throughout the world, so they become a global issue. Some pesticides are an escalating concern worldwide because of their ability to cause reproductive disorders, alterations in endocrine system and cancer. Growing evidence implies that during early life-sensitive stages, the risk of progressionof acute and chronic diseases depends on epigenetic changes by the influence of environmental cues. Several reports deciphered the relationship between exposure to environmental chemicals and epigenetics, and have shown the mechanism that alter the epigenetic states. Changes in global DNA methylation and methylation of specific genes have been described. BecauseDNA methylation influences the binding of transcription factors to DNA, it usually results in a reduction in gene expression. The structure and function of chromatin may be altered by post-translational changes of histone proteins at certain amino acid residues, such as lysine. It is generally believed that acetylation of histones causes transcription to be activated as a result of chromatin relaxation, whereas deacetylation causes gene silencing and transcriptional repression. We performed studies in experimental animals showing that different pesticides can disrupt the expression of early genes in neonates with long term reproductive consequences. We identifiedthat abnormal uterine development was associated with effects on implantation process and epigenetic modifications of critical hormone-dependent genes. Disruption of Hoxa10 and estrogen receptor alpha gene expression was detected in association to changes on DNA methylationand post-translational histone modifications. The evidence indicated that epigenetic modifications are mechanism of action of some EDCs, like pesticides, associated with long term consequences on reproductive health.