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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #341632
Title: Infant formula feeding alters the proliferative status of neonatal mammary glands independent of estrogen signaling

Author
item BHATTACHARYYA, S - Arkansas Children'S Nutrition Research Center (ACNC)
item MERCER, K - Arkansas Children'S Nutrition Research Center (ACNC)
item HENNINGS, L - Arkansas Children'S Nutrition Research Center (ACNC)
item SHARMA, N - Arkansas Children'S Nutrition Research Center (ACNC)
item CHAUDHURY, M - Arkansas Children'S Nutrition Research Center (ACNC)
item YERUVA, L - Arkansas Children'S Nutrition Research Center (ACNC)
item RONIS, MJJ - Arkansas Children'S Nutrition Research Center (ACNC)
item Badger, Thomas - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 2/15/2017
Publication Date: 4/1/2017
Citation: Bhattacharyya, S., Mercer, K.E., Hennings, L., Sharma, N., Chaudhury, M., Yeruva, L., Ronis, M., Badger, T.M. 2017. Infant formula feeding alters the proliferative status of neonatal mammary glands independent of estrogen signaling. Journal of Federation of American Societies for Experimental Biology. 31:792.11.

Interpretive Summary:

Technical Abstract: Soy infant formula contains many phytochemicals, including phytoestrogens, which are structurally similar to estradiol (E2). The mammary gland is particularly sensitive to estrogens, and there are concerns that use of soy-based infant formulas may potentially have adverse effects on mammary tissue development. In this study, we fed female piglets a soy-based infant formula, a dairy milk-based infant formula, or milk formula supplemented with E2, in comparison to piglets receiving sow's breast milk from postnatal day 2-21. Interestingly, we observed a slight but significant increase in terminal end bud number in the mammary glands of the all formula fed groups compared to the sow's milk control. Microarray analysis identified 976 differentially expressed genes between mammary glands from milk formula, soy formula and milk formula supplemented with E2 vs sow fed piglets (+/-1.5 fold, P<0.05). Of these genes, 45% were held in common between all formula groups. E2 supplemented milk formula altered 369 genes. Milk and soy formula altered 45 and 69 genes, respectively, in comparison to the sow's milk control. Functional annotation analysis indicated up-regulation of angiogenesis, adipocyte differentiation, and canonical Wnt signaling pathways in the formula fed groups. Real-time RT-PCR confirmed decreased Wnt10b mRNA expression, and increased Wnt2b, cyclin D and n-myc expression, suggesting an heightened proliferative state in the mammary glands of formula fed piglets compared to piglets receiving sow's milk, P<0.05. Pathways unique to the soy formula group had no apparent relevance to mammary gland development and/or function. Real time RT-PCR expression of the E2-responsive genes progesterone receptor (Pgr) and transforming growth factor beta-2 (Tgfb2) were significantly up-regulated in the E2-supplemented formula group, compared to the milk formula and soy formula groups and the sow's milk control. These data show that dietary exposure to phytoestrogens associated with soy infant formula do not elicit an estrogenic response in the developing mammary gland. However, the neonatal mammary gland is generally quiescent. Our data also suggest that infant formula feeding may initiate proliferative and cell differentiation pathways independent of estrogenic signaling.