Ultrasonographic Patterns of Reproductive Organs in Infants Fed Soy Formula: Comparisons to Infants Fed Breast Milk and Milk Formula

Gilchrist, Janet M.; Moore, Mary B.; Andres, Aline; Estroff, Judy A.; Badger, Thomas M.

doi:10.1016/j.jpeds.2009.08.043

Cited by 56 publications

(45 citation statements)

References 24 publications

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“…E2 treatment resulted in significant decreases in body weight and increases in uterine wet weight. Total serum isoflavone concentrations after feeding SPI were 1.3 g/ml (36), comparable to levels found in infants after soy formula feeding (47). The major serum isoflavone metabolite was equol (20 -40%) followed by genistein (20 -30%) and daidzein (10 -20%).…”

Section: Organ Weights Serum E2 and Isoflavone Levelssupporting

confidence: 64%

“…However, in contrast to data generated with purified isoflavones, there is a long history of safe consumption of soy foods in Asian populations associated with health benefits including reduced risk of estrogen-dependent cancers including breast cancer and even reduced risk of tumor recurrence in breast cancer patients (1-5, 57, 58). Moreover, studies of reproductive organ development in soy formulafed compared with dairy formula-fed and breast-fed infants have observed no significant differences (24,36). Previous studies have suggested that the effects of purified isoflavones, such as genistein and soy products, are different in the mammary gland and that mammary effects of soy products are dependent on how the soy is processed, on developmental stage of exposure, and on the concentrations of endogenous estrogens (2,3,5,32,44,59).…”

Section: Discussionmentioning

confidence: 99%

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Mammary Gland Morphology and Gene Expression Differ in Female Rats Treated with 17β-Estradiol or Fed Soy Protein Isolate

Ronis¹,

Shankar²,

Gómez-Acevedo³

et al. 2012

Endocrinology

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Soy foods have been suggested to have both positive health benefits and potentially adverse effects as a result of their content of phytoestrogens. However, studies on the estrogenicity of soy foods are lacking. Here we directly compared the effects of soy protein isolate (SPI), the protein in soy infant formula, with those of 17β-estradiol (E2), on global gene expression profiles and morphology in the female rat mammary gland. Rats were fed AIN-93G diets containing casein or SPI beginning on postnatal d 30. Rats were ovariectomized on postnatal d 50 and treated with 5 μg/kg/d E2 or vehicle for 14 d. Microarray analysis revealed that E2 treatment altered expression of 780 genes more than or equal to 2-fold (P < 0.05), whereas SPI feeding altered expression of only 53 genes more than or equal to 2-fold. Moreover, the groups had only 10 genes in common to increase more than or equal to 2-fold. The combination of SPI feeding and E2 altered expression of 422 genes and reversed E2 effects on many mRNAs, including those involved in the c-myc signaling pathway, cyclin D1, and Ki67. ERα binding to its response element on the Tie-2/Tek and progesterone receptor promoters was increased by E2, but not SPI, and this promoter binding was suppressed by the combination of E2 + SPI for the Tie-2/Tek promoter but increased for the progesterone receptor promoter (P < 0.05). SPI reduced the ratio of epithelial to fat pad area and E2 + SPI reduced both epithelial and fat pad area (P < 0.05). These data suggest that SPI is only minimally estrogenic in the rat mammary gland even in the absence of endogenous estrogens.

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Section: Organ Weights Serum E2 and Isoflavone Levelssupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Mammary Gland Morphology and Gene Expression Differ in Female Rats Treated with 17β-Estradiol or Fed Soy Protein Isolate

Ronis¹,

Shankar²,

Gómez-Acevedo³

et al. 2012

Endocrinology

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“…This re-evaluation of soy infant formula, which has been in use in the US for over 50 yr and which is consumed by nearly 1 million infants/year, was motivated by a series of in vitro and in vivo results evaluating the estrogenic properties of the soy isoflavone genistein (31). Although epidemiological studies in human infants consuming soy formula revealed normal growth and development (13,55), there is a concern that infants consuming soy formula are exposed to dangerously high levels of genistein and are at increased risk for reproductive tract malformations and for estrogen-sensitive cancers such as breast and uterine cancer, similarly to children of women exposed to diethylstilbestrol in utero (49). Genistein and other soy-associated isoflavone phytochemicals, such as daidzein, and the daidzein metabolite equol have a structural similarity with estrogens and are able to bind weakly to the estrogen receptors alpha and beta (ER␣ and ER␤), with a preference for ER␤ (24,30).…”

mentioning

confidence: 99%

Feeding soy protein isolate and treatment with estradiol have different effects on mammary gland morphology and gene expression in weanling male and female rats

Miousse

Sharma

Blackburn

et al. 2013

Physiological Genomics

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Ronis MJJ. Feeding soy protein isolate and treatment with estradiol have different effects on mammary gland morphology and gene expression in weanling male and female rats. Physiol Genomics 45: 1072-1083. First published September 17, 2013 doi:10.1152/physiolgenomics.00096.2013.-Isoflavones are phytochemical components of soy diets that bind weakly to estrogen receptors (ERs). To study potential estrogen-like actions of soy in the mammary gland during early development, we fed weanling male and female Sprague-Dawley rats a semipurified diet with casein as the sole protein source from postnatal day 21 to 33, the same diet substituting soy protein isolate (SPI) for casein, or the casein diet supplemented with estradiol (E2) at 10 g/kg/day. In contrast to E2, the SPI diet induced no significant change in mammary morphology. In males, there were 34 genes for which expression was changed Ն2-fold in the SPI group vs. 509 changed significantly by E2, and 8 vs. 174 genes in females. Nearly half of SPI-responsive genes in males were also E2 responsive, including adipogenic genes. Serum insulin was found to be decreased by the SPI diet in males. SPI and E2 both downregulated the expression of ER␣ (Esr1) in males and females, and ER␤ (Esr2) only in males. Chromatin immunoprecipitation revealed an increased binding of ER␣ to the promoter of the progesterone receptor (Pgr) and Esr1 in both SPI-and E2-treated males compared with the casein group but differential recruitment of ER␤. ER promoter binding did not correlate with differences in Pgr mRNA expression. This suggests that SPI fails to recruit appropriate co-activators at E2-inducible genes. Our results indicate that SPI behaves like a selective estrogen receptor modulator rather than a weak estrogen in the developing mammary gland.

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“…Although it is clear that pure isoflavones can have estrogenic actions in vitro and in vivo, there is little positive evidence that consumption of soy protein isolate (SPI), which is a complex mixture of proteins and Ͼ100 phytochemicals in addition to isoflavones, results in estrogenic actions in vivo in intact animals having endogenous circulating sex steroids (53). Moreover, there is a paucity of studies examining the potential estrogenicity of soy infant formula feeding in human infants (14,26).…”

mentioning

confidence: 99%

Formula feeding alters hepatic gene expression signature, iron and cholesterol homeostasis in the neonatal pig

Ronis

Chen

Shankar

et al. 2011

Physiological Genomics

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In the U.S. formula feeding remains more popular than breast-feeding. In the current study, neonatal piglets were breast fed and compared with those fed commercially available milk-based formula (milk) or soy-based formula (soy) from postnatal day 2 (PND2) until death at PND21 (the usual age of weaning). Liver weights were greater in formula-fed piglets (P<0.05) than in breast-fed piglets (P<0.05). Affymetrix array analysis revealed significant differences in hepatic gene expression signatures between piglets fed breast milk or formula, as well as between piglets fed milk or soy. In males, expression of 346 hepatic genes differed between formula-fed and breast-fed piglets, and soy-fed differed from milk-fed piglets in 277 genes. Furthermore, gene expression profiles of males differed from females, even when the same diet was consumed. Serum cholesterol was lower in piglets fed formula relative to breast-fed piglets (P<0.05), and this was associated with elevations in mRNA encoding cholesterol 7α-hydroxylase (CYP7A1). Consistent with the human literature, breast-fed piglets had lower hepatic iron accumulation than formula-fed piglets. Hepcidin, a major regulator of hepatic iron trafficking, was elevated in piglets fed formula relative to breast-fed piglets (P<0.05). Female piglets fed soy formula had increased expression of CYP3A enzymes (P<0.05), and soy formula feeding decreased expression of several hepatic genes considered estrogen inducible. These data suggest that: 1) gene expression profiles in neonates differ significantly depending on the diet consumed, 2) hepatic iron storage and cholesterol metabolism clearly differ between breast and formula feeding in piglets, 3) there is no evidence that soy is estrogenic in neonatal pig liver.

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Ultrasonographic Patterns of Reproductive Organs in Infants Fed Soy Formula: Comparisons to Infants Fed Breast Milk and Milk Formula

Cited by 56 publications

References 24 publications

Mammary Gland Morphology and Gene Expression Differ in Female Rats Treated with 17β-Estradiol or Fed Soy Protein Isolate

Mammary Gland Morphology and Gene Expression Differ in Female Rats Treated with 17β-Estradiol or Fed Soy Protein Isolate

Feeding soy protein isolate and treatment with estradiol have different effects on mammary gland morphology and gene expression in weanling male and female rats

Formula feeding alters hepatic gene expression signature, iron and cholesterol homeostasis in the neonatal pig

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