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.
Project description:There are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens. Rat uterus mRNA of ovariectomized adult female rats subject to four different diets (Caseine, Caseine + E2, Soy and Soy+E2 ) were sequenced, in triplicate, in an Illumina GAIIx sequencer.
Project description:This study was designed to determine the effects of plant derived compounds on the transcriptome of estrogen receptor positive breast cancer. Phytoestrogens are compounds produced by plants that possess weak estrogenic activity. They can be found in a wide variety of plants, including fruits and vegetables, but are most abundant in leguminous plants. Legumes are consumed in almost every diet throughout the world, and in addition to the seeds, many other parts of the plant are also edible, including the pods of some varieties. Soybeans have been demonstrated to contain high concentrations of the isoflavones daidzein and genistein, which are re-sponsible for many of the health benefits of soy. Besides isoflavonoids, flavonoids also exert estrogenic activity, but usually at a much lower level of activity compared to that of isoflavonoids. Also, some flavonoids, including kaempferol and quercetin, canexhibit antiestrogenic activity, with several legumes being a source of these flavo-noids. Coumestrol, a coumestan with high estrogenic activity in cell and animal as-says, is also present in several legume seeds and sprouts. These underutilized plant compounds could hold previously unknown potential for antioxidant activity, anti-inflammation activity, cholesterol lowering ability, and even anticancer activity. The goal of the present study was to identify the effects of plant derived compounds on estrogen receptor positive cell line to determine if the compound possess estrogenic or anti-estrogenic activity, thereby highlighting potential implications on human health through diet.
Project description:There are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens.
Project description:The current study directly compared the effects of soy formula feeding with those of estradiol or pure genistein in the neonatal piglet, an animal model which most closely resembles the human infant physiologically and in isoflavone metabolism
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.
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.
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.
Project description:The aim of the study was to decipher metabolisms responsible (i) for the peculiar adaptation of L. plantarum during soy juice fermentation and (ii) for the release of aroma compounds, amino and short-chain fatty acid, and metabolites with health-promoting properties in soy yogurt. The strategy was the sequencing and annotation of a strain (L. plantarum CIRM-BIA777, PRJEB77707) able to degrade galacto- oligosaccharides, the sampling of soy yogurt, RNA-seq to identify differentially expressed genes of L. plantarum and corresponding metabolisms throughout the kinetics of fermentation. Acids and volatile compounds were also quantified.