Long term impact of hypothyrodism during gestation and lactation on the mammary gland

CAMPO VERDE ARBOCCO FIORELLA; PERSIA FABIO ANDRES; ZYLA L; BERNAL NICOLAS; SASSO CV; FLAVIA SANTIANO; GOMEZ SILVINA; BRUNA, F.A.; PISTONE CREYDT VIRGINIA; LOPEZ FONTANA CM; JAHN GA; HAPON MARIA BELEN; CARON RW

Journal of Developmental Origins of Healt and Disease

Cambridge University Press

Año: 2022

2040-1744

The functional differentiation of the mammary gland (MG) is fundamental for the preventionof mammary pathologies. This process occurs throughout pregnancy and lactation, makingthese stages key events for the study of pathologies associated with development and differentiation. Many studies have investigated the link between mammary pathologies and thyroiddiseases, but most have ignored the role of thyroid hormone (TH) in the functional differentiation of the MG. In this work, we show the long-term impact of hypothyroidism in an animalmodel whose lactogenic differentiation occurred at low TH levels. We evaluated the ability ofthe MG to respond to hormonal control and regulate cell cycle progression. We found that adeficit in TH throughout pregnancy and lactation induces a long-term decrease in Rb phosphorylation, increases p53, p21, Cyclin D1 and Ki67 expression, reduces progesterone receptorexpression, and induces nonmalignant lesions in mammary tissue. This paper shows the importance of TH level control during mammary differentiation and its long-term impact on mammary function.