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

Published online by Cambridge University Press:  07 June 2022

Fiorella Campo Verde Arboccó Open the ORCID record for Fiorella Campo Verde Arboccó [Opens in a new window] ,
Fabio A. Persia ,
Leila Zyla ,
Nicolás Bernal ,
Verónica C. Sasso ,
Flavia Santiano ,
Silvina Gomez ,
Flavia Bruna ,
Virginia Pistone-Creydt  and
Constanza Lopez-Fontana
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Fiorella Campo Verde Arboccó*
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina Universidad de Mendoza, Facultad de Ciencias Médicas, Mendoza, Argentina
Fabio A. Persia
Affiliation:
Universidad de Mendoza, Facultad de Ciencias Médicas, Mendoza, Argentina
Leila Zyla
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina
Nicolás Bernal
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina
Verónica C. Sasso
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina
Flavia Santiano
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina
Silvina Gomez
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina
Flavia Bruna
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina
Virginia Pistone-Creydt
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina
Constanza Lopez-Fontana
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina
Graciela A. Jahn
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina
María Belén Hapon
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, Argentina
Ruben W. Carón
Affiliation:
Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CONICET 5500 Mendoza Argentina – Universidad Nacional de Cuyo, Mendoza, Argentina
*
Address for correspondence: Dr. Fiorella Campo Verde Arbocco, Imbecu Conicet, C.C. 855, 5500 Mendoza, Argentina. Fax: 54 261 5244001. Emails: [email protected], [email protected]
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Abstract

The functional differentiation of the mammary gland (MG) is fundamental for the prevention of mammary pathologies. This process occurs throughout pregnancy and lactation, making these stages key events for the study of pathologies associated with development and differentiation. Many studies have investigated the link between mammary pathologies and thyroid diseases, 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 animal model whose lactogenic differentiation occurred at low TH levels. We evaluated the ability of the MG to respond to hormonal control and regulate cell cycle progression. We found that a deficit in TH throughout pregnancy and lactation induces a long-term decrease in Rb phosphorylation, increases p53, p21, Cyclin D1 and Ki67 expression, reduces progesterone receptor expression, 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.

Keywords

Mammary differentiationhypothyroidismcell cyclelong-term impact
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 14 , Issue 1 , February 2023 , pp. 122 - 131
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Copyright
© The Author(s), 2022. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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Footnotes

Fiorella Campo Verde Arboccó and Fabio A. Persia are the equal collaborators.

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