Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats

Abstract

There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 μg/kg/d 17β-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05). RNAseq analysis revealed that E2 significantly altered expression of 1991 uterine genes (P<0.05). SPI feeding had no effect on uterine weight and altered expression of far fewer genes than E2 at 152 genes (P<0.05). Overlap between E2 and SPI genes was limited to 67 genes. Functional annotation analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of estrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (P<0.05). These data suggest that SPI is a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens.

Effects of soy containing diet and isoflavones on cytochrome P450 enzyme expression and activity

“…This was accompanied by reduced expression of AhR protein and its heterodimerization partner ARNT (Rowlands et al 2001). In contrast, no differences were observed in inducibility of CYP1A1 and CYP1B1 in the uterus of female rats fed casein or SPI and treated with DMBA (Ronis et al 2016). Also in contrast to data in rats, no significant change in expression of CYP1A1 or CP1B1 was observed in the mammary gland of ovariectomized female cynomolgus macaques fed soy diets with or without bound phytochemicals for 36 months (Scott et al 2008).…”

“…al. 2009, Ronis et al, 2011a) or in estrogen-sensitive reproductive tissues such as the mammary, uterus or testis (Ronis et al, 2012; Miousse et al, 2013; Ronis et al, 2014; Ronis et al, 2016). These data suggest that although studies on the effects of pure isoflavones on CYP expression and activity may be of importance in consumers of isoflavone supplements, they probably have limited relevance to soy consumers.…”

RNA-sequencing data analysis of uterus in ovariectomized rats fed with soy protein isolate, 17β-estradiol and casein

“…Uteri were collected and frozen at −80 °C until analysis. Treatment groups ( N =6/group), were designed as follows: 1) Control, CAS diet (CAS); 2) CAS-E2, E2 treatment on CAS background; 3) SPI, SPI diet; 4) SPI-E2, E2 treatment on SPI background [1] .…”

“…Additional functional annotation analysis of KEGG pathways is also presented for each treatment, together with networks of interaction between those pathways. Further interpretation and discussion of this data can be found in the article “Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats” Ronis et al (2016) [1] .…”

Effects of standard diets from different sources on growth and some organ parameters of rats

“…The variety of feed materials used in the production of laboratory animal diets may create differences in nutrient composition. Even if the nutrient values of the diets are provided at an appropriate level, the differences in macro and micro nutrient levels may affect the animal health and performance (Andreoli et al, 2016;Nagano et al, 2016;Ronis et al, 2016;Genç, 2017). The diets produced with closed-formula -those are not reporting of micro-nutrients and raw materials or not conforming to the standards-appear to be a greater risk to influence the result of the research.…”