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The epigenetic role of breastfeeding in mammary differentiation

Published online by Cambridge University Press:  07 October 2020

Flavia E. Santiano ,
Fiorella Campo Verde Arboccó ,
Flavia A. Bruna ,
Leila E. Zyla ,
Corina V. Sasso ,
Silvina Gómez ,
Virginia Pistone-Creydt ,
Constanza M. López-Fontana  and
Rubén W. Carón Open the ORCID record for Rubén W. Carón [Opens in a new window]
Flavia E. Santiano
Affiliation:
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo, IMBECU, CONICET UNCuyo, Mendoza, Argentina
Fiorella Campo Verde Arboccó
Affiliation:
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo, IMBECU, CONICET UNCuyo, Mendoza, Argentina Physiology Department, School of Medicine, University of Mendoza, Mendoza, Argentina
Flavia A. Bruna
Affiliation:
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo, IMBECU, CONICET UNCuyo, Mendoza, Argentina
Leila E. Zyla
Affiliation:
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo, IMBECU, CONICET UNCuyo, Mendoza, Argentina Physiology Department, School of Medicine, University of Mendoza, Mendoza, Argentina
Corina V. Sasso
Affiliation:
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo, IMBECU, CONICET UNCuyo, Mendoza, Argentina
Silvina Gómez
Affiliation:
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo, IMBECU, CONICET UNCuyo, Mendoza, Argentina
Virginia Pistone-Creydt
Affiliation:
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo, IMBECU, CONICET UNCuyo, Mendoza, Argentina
Constanza M. López-Fontana
Affiliation:
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo, IMBECU, CONICET UNCuyo, Mendoza, Argentina
Rubén W. Carón*
Affiliation:
Laboratory of Hormones and Cancer Biology, Institute of Medicine and Experimental Biology of Cuyo, IMBECU, CONICET UNCuyo, Mendoza, Argentina
*
Address for correspondence: Rubén Walter Carón, Laboratorio de Hormonas y Biología del Cáncer, IMBECU, CONICET, CCT-Mendoza. Av. Adrián Ruiz-Leal s/n, CC855, Mendoza, Argentina. Email: [email protected]
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Abstract

Maternal milk consumption can cause changes in the mammary epithelium of the offspring that result in the expression of molecules involved in the induction of differentiation, reducing the risk of developing mammary cancer later in life. We previously showed that animals that maintained a higher intake of maternal milk had a lower incidence of mammary cancer. In the present study, we evaluated one of the possible mechanisms by which the consumption of maternal milk could modify the susceptibility to mammary carcinogenesis. We used Sprague Dawley rats reared in litters of 3 (L3), 8 (L8), or 12 (L12) pups per mother in order to generate a differential consumption of milk. Whole mounts of mammary glands were performed to analyze the changes in morphology. Using real-time polymerase chain reaction (PCR), we analyzed the expression of mammary Pinc, Tbx3, Stat6, and Gata3 genes. We use the real-time methylation-specific polymerase chain reaction method to assess the methylation status of Stat6 and Gata3 CpG sites. Our findings show an increase in the size of the epithelial tree and a smaller number of ducts called terminal end buds in L3 vs. L12. We observed an increased expression of mRNA of Stat6, Gata3, Tbx3, and a lower expression of Pinc in L3 with respect to L12. Stat6 and Gata3 are more methylated in the CpG islands of the promoter analyzed in L12 vs. L3. In conclusion, the increased consumption of maternal milk during the postnatal stage generates epigenetic and morphological changes associated with the differentiation of the mammary gland.

Keywords

Postnataldevelopmentlactationmammary glandTEBs
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 4 , August 2021 , pp. 578 - 586
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Copyright
© The Author(s), 2020. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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