The epigenetic role of breastfeeding in mammary differentiation

BRUNA, FLAVIA A.; GÓMEZ, SILVINA; CARÓN, RUBÉN W.; SANTIANO, FLAVIA E.; ZYLA, LEILA E.; PISTONE-CREYDT, VIRGINIA; CAMPO VERDE ARBOCCÓ, FIORELLA; SASSO, CORINA V.; LÓPEZ-FONTANA, CONSTANZA M.

Journal of Developmental Origins of Health and Disease

Cambridge University Press

Lugar: Cambridge; Año: 2020 p. 1 - 9

2040-1744

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 higher intake of maternal milk had 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 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 TEBs in L3 vs. L12. We observed an increased expression of mRNA of Stat6, Gata3, TBX3 and a lower expression of Pinc in L3 respect to L12. Stat6 and Gata3 are more methylated in the CpG islands of the promoter analysed in L12 vs. L3. In conclusion, the increased consumption of maternal milk during the postnatal stage generates epigenetic and morphological changes associated to differentiation of the mammary epithelium.