HYPOTHYROIDISM, LACTATION AND MAMMARY MICRO-RNAs; THE LINK BETWEEN A LOCAL PATHOLOGY AND THE MAMMARY EPIGENOME.

CAMPO VERDE ARBOCCO, F.; MICHEL, M.C.; ZYLA, L.E.; CARON, R.W

Mendoza

Congreso; XXXIX Reunión Cientifica Anual de la Sociedad de Biología de Cuyo; 2021

Sociedad de Biología de Cuyo

Lactation is the gold standard of mammary differentiation. The hormonal environment of gestation and lactation promotes histologic and epigenetics changes in mammary tissue. The epigenetic imprinting is conserved beyond the weaning into mammary stem cell who survives the involution and inherit its epigenome to new population of mammary epithelial cell. Mammary differentiation is necessary for prevention of mammary pathologies. Any alteration of mammary differentiation may expose it to pathological development. In previous work we show that thyroid hormone deficiency through gestation and lactation alters the mammary differentiation, has a long-term impact in mammary control of cell cycle, induce methylation changes on mammary differentiation genes and induce non-malignant mammary lesion. GATA-3 is a mammary differentiation central gene which was particularly affected by thyroid hormone deficiency since its promotor methylation level strongly decreased but also decreased its mRNA expression. The Micro-ARNs (miRNAs) are small non-coding RNAs which regulate the gene expression. Mammary differentiation involves the expression of many miRNAs, some of them related to mammary pathologies development. In this work we investigated the mammary glands of hypothyroid Sprague Dawley hypothyroid (HypoT) and euthyroid (Ctrl) rats that have undergone a complete cycle of gestation, lactation and involution. On day 28 after weaning, we dissected the inguinal mammary glands and using steem loop real time PCR analyzed the expression of miRNAs related to mammary differentiation and mammary pathologies develop: rno-200a-3p, rno-206-3p, rno-27b-3p and Let7. We found that the thyroid hormone deficiency in gestation and lactation, induce long term changes in miRNAs expression. Especially, we found that the thyroid hormone deficit, induce a long-term increase of rno-206-3p expression level, a miRNA related to GATA-3 expression. Added to our previous results, these findings proved that the thyroid hormone deficiency through gestation and lactation alter the mammary epigenome establishment in mechanism that includes the expression of miRNAs related to mammary differentiation.