Transgenerational Effects of Early Exposure to Soy Isoflavones on Reproductive Health and Bone Development in CD-1 Mice (original) (raw)
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International journal of environmental research and public health, 2016
Over the past decade, our research group has characterized and used a mouse model to demonstrate that "nutritional programming" of bone development occurs when mice receive soy isoflavones (ISO) during the first days of life. Nutritional programming of bone development can be defined as the ability for diet during early life to set a trajectory for better or compromised bone health at adulthood. We have shown that CD-1 mice exposed to soy ISO during early neonatal life have higher bone mineral density (BMD) and greater trabecular inter-connectivity in long bones and lumbar spine at young adulthood. These skeletal sites also withstand greater forces before fracture. Because the chemical structure of ISO resembles that of 17-β-estradiol and can bind to estrogen receptors in reproductive tissues, it was prudent to expand analyses to include measures of reproductive health. This review highlights aspects of our studies in CD-1 mice to understand the early life programming effe...
Menopause, 2005
Objective: The present study was conducted to determine the effects of dietary soy protein and isoflavones on bone and the reproductive tract in the absence of the ovary. Design: Three-month-old Sprague-Dawley rats (n = 56) were either sham-operated or ovariectomized and then fed diets containing casein or soy protein ± isoflavone extract for 12 weeks. The amounts of casein, soy protein, and extract (per kg diet) in each group were as follows: (1) Ovariectomy, 200 g of casein; (2) Ovariectomy+low soy, 100 g of casein + 100 g of soy protein; (3) Ovariectomy+high soy, 200 g of soy protein; (4) Ovariectomy+low extract, 200 g of casein + 17.2 g of extract; (5) Ovariectomy+high extract, 200 g of casein + 34.4 g of extract; (6) Ovary intact, 200 g of casein; (7) Ovariectomy+estradiol-17b, 200 g of casein. Diet consumption, body weight, uterine weight, urine deoxypyridinoline, and bone mineral density of the femur and lumbar vertebrae were measured. The femur rigidity was evaluated by histomorphometry. The reproductive tract (uterus, vagina, and cervix) was studied histologically. Results: The Ovariectomy group showed significant increases in body weight, diet consumption, and deoxypyridinoline, decreases in uterine weight and bone mineral density, and negative changes in histomorphometry compared with the Ovary intact group. Neither soy protein nor extract diets abrogated these alterations, except for the Ovariectomy+high extract group that showed statistically significant positive changes in histomorphometric parameters. There were no histological differences in the reproductive tract among Ovariectomy, Ovariectomy+soy, and Ovariectomy+extract groups. The estradiol-17b replacement abrogated ovariectomy-induced alterations. Conclusion: Dietary intake of isoflavones by sexually mature ovariectomized rats has a minimal beneficial effect on bone with no effect on the reproductive tract.
Osteoporosis International, 2007
Introduction Soy products are of particular interest because of their potential health benefits in a range of hormonal conditions, such as osteoporosis, due to their high content in phytoestrogens. Because equol, the main metabolite from soy isoflavones, is thought to be powerful, the present study was designated to evaluate the bone-sparing effects of equol by either providing the molecule through the diet or by eliciting its endogenous production by modulating intestinal microflora by short-chain fructooligosaccharides (sc-FOS) or live microbial (Lactobacillus casei) together with daidzein, its precursor. Methods A comparison with daidzein and genistein was also performed. Rats (3 months old) were ovariectomised (OVX) or sham-operated (SH). Ovariectomised rats were randomly assigned to six experimental diets for 3 months: a control diet (OVX), the control diet supplemented with either genistein (G), or daidzein (D), or equol (E) at the level of 10 μg/g body weight/d. The remaining OVX rats were given daidzein at the dose of 10 μg/g body weight/d, simultaneously with short-chain FOS (Actilight®, Beghin-Meiji) (D+FOS) or Lactobacillus casei (Actimel, Danone) (D+L). The SH rats were given the same control diet as OVX. Results Genistein, daidzein or equol exhibited a bone sparing effect. Indeed, total femoral bone mineral density (BMD) was significantly enhanced (compared to that of OVX rats), as was the metaphyseal compartment. Bone strength was improved by E consumption, but not by genistein or daidzein given alone. As far as the FOS diet is concerned, the addition of prebiotics significantly raised efficiency of the daidzein protective effect on both femoral BMD and mechanical properties. The effects of lactobacillus were similar, except that the increase in metaphyseal-BMD was not significant. Conclusion In conclusion, long-term equol consumption, like genistein and daidzein, in the ovariectomized rat, provides bone sparing effects. Adding indigestible sugars, such as FOS or live microbial as L. casei, in the diet significantly improves daidzein protective effects on the skeleton.
Journal of Functional Foods, 2014
In a longitudinally designed study, we tested whether an isoflavone enriched soy extract (SE) stimulated peak bone gain in rats during growth and maturity so as to confer better bone conserving effect after ovariectomy with concurrent treatment discontinuation. Weaned female rats were given SE or vehicle for 12-weeks and bone parameters were recorded (baseline). One group was then ovariectomized (OVx) and the other group sham operated. Vehicle group after OVx was given 17b-estradiol (E2) or continued with vehicle (OVx + vehicle). SE group after OVx was given vehicle (SEV). After 12-weeks, all groups were killed (endpoint). At baseline, SE group had greater cortical bone parameters over control. At endpoint, SEV group displayed significant bone conservation which was comparable to OVx + E2 group. Data suggest that SE enhanced peak bone accrual that supported skeletal preservation post-OVx on a par with E2 supplementation, not withstanding SE withdrawal at OVx.
The American Journal of Clinical Nutrition
Our previous studies showed that a soy-protein diet prevents ovariectomy-induced bone loss. The purpose of this study was to determine whether isoflavones in soy protein are responsible for this bone-protective effect. Forty-eight 95-d-old Sprague-Dawley rats were divided into 4 groups: sham-operated fed a casein-based diet (SHAM), ovariectomized fed a caseinbased diet (OVX+CASEIN), ovariectomized fed soy protein with normal isoflavone content (OVX+SOY), and ovariectomized fed soy protein with reduced isoflavone content (OVX+SOYϪ). The OVX+SOY group had significantly greater femoral bone density (in g/cm 3 bone vol) than the OVX+CASEIN group, whereas OVX+SOYϪ was similar to OVX+CASEIN (x-± SD; SHAM, 1.522 ± 0.041; OVX+CASEIN, 1.449 ± 0.044; OVX+SOY, 1.497 ± 0.030; OVX+SOYϪ, 1.452 ± 0.030). Ovariectomy resulted in greater bone turnover as indicated by higher serum alkaline phosphatase activity, serum insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations, and urinary hydroxyproline. These increases were not affected by soy with either normal or reduced isoflavone content. Similarly, histomorphometry revealed a greater bone formation rate with ovariectomy, and this was not altered by the soy diets. The findings of this study suggest that isoflavones in soy protein are responsible for its bone-sparing effects. Further studies to evaluate the mechanism of action of isoflavones on bone are warranted.
Nutrition, 2011
Objective: This study aimed to determine the influence of high-dose soy isoflavones (daidzein and genistein) administered from prenatal life to sexual maturity on testosterone and estradiol levels, testicular and epididymal morphology, the number of epididymal spermatozoa, and mineral metabolism in rats. Methods: Pregnant Wistar rats received orally soy isoflavones, daidzein, and genistein at a dose of 200 mg/kg of body weight per day. After separating sucklings from their mothers, male rats received the same dose of isoflavones until reaching the age of sexual maturity, i.e., for 3 mo. Results: In the isoflavone-treated group, statistically significant decreased concentrations of zinc (determined using atomic absorption spectrophotometry) in blood serum and increased concentrations in bone were observed. The isoflavones induced changes in the morphology of the seminiferous epithelium of rat testes. However, there were no significant changes in the number of spermatozoa in the epididymis. The levels of estradiol in serum and cauda epididymis homogenates of rats receiving phytoestrogens were significantly higher than in the control group. No differences were observed in testosterone concentrations in the serum of treated and control rats. The testosterone levels in the homogenates of the treated rat testes were significantly lower than in the control group. Conclusion: The relatively mild effects of phytoestrogen administration on the morphology of testes and epididymides and the number of epididymal spermatozoa were observed despite the high dose used. The exposure of rats to genistein and daidzein during intrauterine life until sexual maturity influenced the mineral metabolism of the organism by significant decreases of Zn concentration in serum and increased Zn concentration in bones.
Advances in reproductive sciences, 2017
Chemically, soy contains a group of phytoestrogens called isoflavones, predominantly genistein and daidzein. The aim of the present study was to determine the effects of post weaning consumption of dietary soy isoflavones on prepubertal and postpubertal serum levels of some reproductive hormones of male Wistar rats. The study involved investigating the effects of different doses of isoflavones in the diet. Male rats were weaned on either soy isoflavone free diet or on isoflavone containing diets, formulated by adding increasing amounts of Novasoy, a commercially available isoflavone supplement to the isoflavone free diet to give varying concentrations of isoflavones. Three isoflavone containing diets were used and these had 74.5, 235.6 and 1046.6 mg total isoflavones/kg pelleted diet. These diets represented the isoflavone concentration lower, equal to and more than that found in soy-based infant formulas respectively. The results obtained showed that; administration of low doses soy isoflavones (74.5 mg/kg) produced significant (p < 0.05) increase in serum Antimullerian Hormone levels both in prepubertal and post pubertal rats, when compared to the control groups. Administration of moderate doses of isoflavones (235.6 mg/kg) produced significant (p < 0.05) increase in serum levels of Antimullerian Hormone and Inhibin in both prepubertal and post pubertal rats when compared to the control groups. Administration of high doses of isoflavones (1046.6 mg/kg) produced significant (p < 0.05) increase in serum levels of Inhibin in both prepubertal and post pubertal rats when compared to the control groups. From this study, it was concluded that post-weaning consumption soy isoflavones produced significant changes