Soy Infant Formula Is Not Estrogenic or Results in Reproductive Toxicity in Male Piglets
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ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE168627 | GEO | 2021/03/31
REPOSITORIES: GEO
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Project description:The majority of babies in the US are formula-fed instead of breast fed. There are major differences in the composition of formulas and breast milk and yet little is known about metabolic differences in babies as the result of feeding these very different diets and how that might affect development or disease risk in later life. One concern is that soy-based formulas might have adverse health effects in babies as a result of the presence of low levels of estrogenic phytochemicals – genistein and daidzein which are normally present in soy beans. In the current study, we used a piglet model to look at this question. Piglets were either fed breast milk from the sow or were fed two different infant formulas (cow’s milk-based or soy-based) from age 2 days to 21 days when pigs are normally weaned onto solid food. Blood glucose and lipids were measured. Formula-fed pigs were found to have lower cholesterol than breast fed piglets and in addition had larger stores of iron in their liver.Microarray analysis was carried out to see if changes in liver gene expression could explain these effects of formula feeding. It was found that overall gene expression profiles were influenced by formula feeding compared to breast fed neonates. Gender-independent and unique effects of formula influenced cholesterol and iron metabolism. Further, soy formula feeding in comparison to milk-based formula failed to reveal any estrogenic actions on hepatic gene expression in either male or female pigs.
2012-01-05 | GSE28349 | GEO
Project description:The majority of babies in the US are formula-fed instead of breast fed. There are major differences in the composition of formulas and breast milk and yet little is known about metabolic differences in babies as the result of feeding these very different diets and how that might affect development or disease risk in later life. One concern is that soy-based formulas might have adverse health effects in babies as a result of the presence of low levels of estrogenic phytochemicals genistein and daidzein which are normally present in soy beans. In the current study, we used a piglet model to look at this question. Piglets were either fed breast milk from the sow or were fed two different infant formulas (cow's milk-based or soy-based) from age 2 days to 21 days when pigs are normally weaned onto solid food. Blood glucose and lipids were measured. Formula-fed pigs were found to have lower cholesterol than breast fed piglets and in addition had larger stores of iron in their liver.Microarray analysis was carried out to see if changes in liver gene expression could explain these effects of formula feeding. It was found that overall gene expression profiles were influenced by formula feeding compared to breast fed neonates. Gender-independent and unique effects of formula influenced cholesterol and iron metabolism. Further, soy formula feeding in comparison to milk-based formula failed to reveal any estrogenic actions on hepatic gene expression in either male or female pigs. Piglets (female, male) were either fed breast milk from the sow or were fed two different infant formulas (cow's milk-based or soy-based) from age 2 days to 21 days when pigs are normally weaned onto solid food.
2012-01-05 | E-GEOD-28349 | biostudies-arrayexpress
Project description:Soy Infant Formula Is Not Estrogenic or Results in Reproductive Toxicity in Male Piglets
| PRJNA713299 | ENA
Project description:To understand the complex mechanism of estrogen action, multiple assays based on different biological principles is important. Here, multiple assays based on cell, protein and transcription assays were used to evaluate estrogenic activity of soymilk extracts before and after fermentation, and four soy compounds, genistein and daidzein, and their glycosides, genistin and daidzin, respectively. The data obtained by a transcription assay, RNA-sequencing (RNA-seq), was further examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis to understand cell functions, i.e. biological processes and metabolic pathways. Among the cell functions identified, the sets of genes for cell division/cell cycle and DNA replication/DNA repair are significantly up-regulated, whereas those for autophagy are significantly down-regulated, which explains well the enhanced activity of cell proliferation by these materials. The applications of estrogenic activity of soymilk extracts and soy flavonoids, and the contribution of fermentation, include pharmacological benefits, such as bone protection/bone regeneration, cancer chemoprevention, neuroprotection and the treatment of menopausal syndromes.
2023-10-31 | GSE226627 | GEO
Project description:Intrauterine growth restriction is a common cause of small for gestational age (SGA) infants worldwide. SGA infants are deficient in digestive enzymes required for fat digestion and absorption compared to appropriate for gestational age (AGA), putting them at risk for impaired neurocognitive development. The objective was to determine if a hydrolyzed fat (HF) infant formula containing soy free fatty acids, 2-monoacylglycerolpalmitate, cholesterol, and soy lecithin could increase brain tissue incorporation of essential fatty acids or white matter to enhance brain development in SGA and AGA neonatal piglet models. Sex-matched, littermate pairs of SGA (0.5-0.9kg) and AGA (1.2-1.8kg) 2 day old piglets (N=60) were randomly assigned to control (CON) or HF formula diets in a 2 x 2 factorial design. On day 14, 24 piglets were used for hippocampal RNA-sequencing; the rest began a spatial learning task. On days 26-29, brain structure was assessed by magnetic resonance imaging (MRI). Cerebellum and hippocampus were analyzed for fatty acid content. SGA piglets grew more slowly than AGA piglets, with no effect of diet on daily weight gain or weight at MRI. HF diet did not affect brain weight. HF diet increased relative volumes of 7 brain regions and white matter (WM) volume in both SGA and AGA piglets. However, HF did not ameliorate SGA total WM integrity deficits. RNA sequencing revealed SGA piglets had increased gene expression of synapse and cell signaling pathways and decreased expression of ribosome pathways in the hippocampus compared to AGA. HF decreased expression of immune response related genes in the hippocampus of AGA and SGA piglets, but did not correct gene expression patterns in SGA piglets. Piglets learned the T-maze task at the same rate, but SGA HF, SGA CON, and AGA HF piglets had more accurate performance than AGA CON piglets on reversal day 2. HF increased arachidonic acid (ARA) percentage in the cerebellum and total ARA in the hippocampus. HF enhanced brain development in the neonatal piglet measured by brain volume and WM volume in specific brain regions; however, more studies are needed to assess long-term outcomes.
2020-02-06 | GSE134739 | GEO
Project description:The role of diet in the prevention of breast cancer is widely accepted, yet little is known on how early dietary effects mitigate adult cancer risk. Soy consumption is associated with reduced breast cancer risk in women, an effect largely attributed to the soy isoflavone genistein (GEN). We previously showed lower chemically-induced mammary tumor incidence in young adult rats with lifetime dietary intake of soy protein isolate (SPI), a highly refined soy product in infant formula, than in those fed the control diet Casein (CAS). To gain insight into signaling pathways underlying dietary tumor protection, we performed genome-wide expression profiling of mammary epithelial cells from young adult rats lifetime fed CAS, SPI, or supplemental GEN-based diets. We identified mammary epithelial genes regulated by SPI (79 total) and GEN (99 total) using Affymetrix rat 230A GeneChip arrays and found minimal overlap in gene expression patterns. We showed that the regulated transcripts functionally cluster in biochemical pathways involving metabolism, immune response, signal transduction, and ion transport. We confirmed the differential expression of Wnt (Wnt5a, Sfrp2) and Notch (Notch2, Hes1) signaling components by SPI and/or GEN using QPCR. Wnt pathway inhibition by GEN was supported by lower Cyclin D1 immunoreactivity in mammary ductal epithelium of GEN relative to CAS and SPI, despite their comparable levels of membrane-localized E-cadherin and β-catenin. Identification of distinct GEN and SPI responsive genes in mammary epithelial cells may define early events contributing to tumor protection by diet relevant to the prevention of breast and other types of cancer. Experiment Overall Design: Female Sprague-Dawley rats, fed one of the three purified diets, were studied at postnatal day50. Total RNA( each RNA samples were extracted from #4 mammary gland from two animals under the same diet group) purified from non-tumor tissue within the proximal half of each colon, was used to prepare biotinylated probes, which were hybridized to Affymetrix RAE230 rat microarrays.
2007-11-29 | E-GEOD-6879 | biostudies-arrayexpress
Project description:Powder Infant formula Genome sequencing and assembly
| PRJNA795891 | ENA
Project description:Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer. Genome-wide expression analysis was performed on breast cancer tissue from women following treatment with soy (n=28) or placebo (n=23).
2014-07-01 | E-GEOD-58792 | biostudies-arrayexpress
Project description:Background There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways. Methods Women (n = 140) with early-stage breast cancer were randomized to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString inin pre- and post-treatment tumor tissue. Genome-wide expression analysis was performed on post-treatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry. Results Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and post-treatment samples, 21 genes (out of 202) showed altered expression (two-sided Student’s t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student’s t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2 fold) of cell cycle transcripts, including those which promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3. Conclusions Gene expression associated with soy intake and high plasma genistein define a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer.
2014-07-01 | GSE58792 | GEO
Project description:Scope: Soy flour diet (MS) prevented isoflavones from stimulating MCF-7 tumor growth in athymic nude mice, indicating that other bioactive compounds in soy can negate the estrogenic properties of isoflavones. The underlying signal transduction pathways to explain the protective effects of soy flour consumption were studied here. Methods and results: Ovariectomized athymic nude mice inoculated with MCF-7 human breast cancer cells were fed either MS or purified isoflavone mix (MI), both with equivalent amounts of genistein. Positive controls received estradiol pellets and negative controls received sham pellets. GeneChip-Human-Genome-U133 Plus-2.0 Array platform was used to evaluate gene expressions, and results were analyzed using bioinformatics approaches. Tumors in MS-fed mice exhibited higher expression of tumor-growth-suppressing genes ATP2A3 and BLNK, and lower expression of oncogene MYC. Tumors in MI-fed mice expressed higher level of oncogene MYB and lower level of MHC-I and MHC-II, allowing tumor cells to escape immunosurveillance. MS-induced gene expression alterations were predictive of prolonged survival among estrogen-receptor-positive breast cancer patients, whilst MI-induced gene changes were predictive of shortened survival. Conclusion: Our findings suggest dietary soy flour affects gene expression differently than purified isoflavones, which may explain why soy foods prevent isoflavones-induced stimulation of MCF-7 tumor growth in athymic nude mice.
2016-11-23 | GSE63205 | GEO