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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #360027

Title: Effects of infant formula feeding on neonatal mammary gland development

item LIN, HAIXIA - University Arkansas For Medical Sciences (UAMS)
item CHAUDHURY, MOUSUMI - Arkansas Children'S Nutrition Research Center (ACNC)
item SHARMA, NEHA - Arkansas Children'S Nutrition Research Center (ACNC)
item BHATTACHARYYA, SUDEEPA - University Arkansas For Medical Sciences (UAMS)
item YERUVA, LAXMI - Arkansas Children'S Nutrition Research Center (ACNC)
item RONIS, MARTIN - Louisiana State University Medical Center
item MERCER, KELLY - University Arkansas For Medical Sciences (UAMS)

Submitted to: Society of Toxicology
Publication Type: Abstract Only
Publication Acceptance Date: 11/27/2018
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Soy formulas contain isoflavones, which are structurally similar to estradiol (E2). Given the mammary gland is sensitive to estrogens, there are concerns that soy formula feeding may promote premature mammary development. In this study, we used a neonatal piglet model to identify changes in early mammary gland development in response to different postnatal diets. Groups of female piglets (n=6/group) were fed cow's milk formula (Milk), soy formula (Soy), or breastfed with the sow (Sow) from postnatal day 2-21. To assess directly the effects of estrogen or isoflavone on mammary development, additional groups were fed Milk supplemented with estradiol (Milk+E2) or with genistein (Milk+G). In the Milk+E2 group, serum E2 concentration was significantly higher (10- to 20-fold) relative to other diet groups. Terminal end bud numbers were significantly increased in the Milk, Soy and Milk+G groups relative to Sow or Milk+E2 groups. Microarray analysis identified 130, 253, 125, and 170 differentially-expressed transcripts (±2-fold, P<0.05) between Milk, Milk+E2, Milk+G and Soy groups, respectively, relative to the Sow group. Functional annotation analysis indicated formula feeding alters gene expression in pathways associated with cell proliferation and apoptosis. Additional pathways that were identified, cell morphogenesis and differentiation and hormone response, were only associated with the Milk+E2 group. We also confirmed several down-regulated microRNAs including miR-128, miR-1 and miR-422b (2.4- to 10.2-fold) in the formula groups compared to the Sow control; these have been implicated in regulation of cellular apoptosis and proliferation. The changes in mRNA expression of Wnt2b, cyclin D and n-myc indicated a heightened proliferative state in mammary glands of all formula groups compared to the Sow group. E2-responsive genes, Pgr, Tgfb2, Rerg, were significantly upregulated in the Milk+E2 group relative to all other groups. Our data suggest that dietary exposure to soy isoflavones during infant feeding does not elicit an estrogenic response in the mammary gland. Still, formula feeding may initiate proliferative pathways independent of estrogenic signaling.