Dataset Information

Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study.

ABSTRACT: Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White-Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17-beta-estradiol (2 mg/kg/d) (M + E2) or supplemented with genistein (84 mg/L of diet; (M + G) from postnatal day 2 until day 21. E2 treatment reduced testis weight (p < 0.05) as percentage of body weight, significantly suppressed serum androgen concentrations, increased tubule area, Germ cell and Sertoli cell numbers (p < 0.05) relative to those of Sow or Milk groups. Soy formula had no such effects relative to Sow or Milk groups. mRNAseq revealed 103 differentially expressed genes in the M + E2 group compared to the Milk group related to endocrine/metabolic disorders. However, little overlap was observed between the other treatment groups. These data suggest soy formula is not estrogenic in the male neonatal piglet and that soy formula does not significantly alter male reproductive development.

SUBMITTER: Ronis MJJ

PROVIDER: S-EPMC8912539 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study.

Ronis Martin J J MJJ Gomez-Acevedo Horacio H Shankar Kartik K Hennings Leah L Sharma Neha N Blackburn Michael L ML Miousse Isabelle I Dawson Harry H Chen Celine C Mercer Kelly E KE Badger Thomas M TM

Nutrients 20220307 5

Soy infant formula which is fed to over half a million infants per year contains isoflavones such as genistein, which have been shown to be estrogenic at high concentrations. The developing testis is sensitive to estrogens, raising concern that the use of soy formulas may result in male reproductive toxicity. In the current study, male White-Dutch Landrace piglets received either sow milk (Sow), or were provided milk formula (Milk), soy formula (Soy), milk formula supplemented with 17-beta-estra ...[more]

PMID: 35268101

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Project description:The isoflavone phytoestrogens found in the soy protein isolate used in soy infant formulas have been shown to have estrogenic actions in the developing male reproductive tract resulting in reproductive toxicity. However, few studies have examined potential estrogenicity of soy protein isolate as opposed to that of pure isoflavones. In this study, we fed weanling male Sprague-Dawley rats a semi-purified diet with casein or soy protein isolate as the sole protein source from postnatal day 21 to 33. Additional groups were fed casein or soy protein isolate and treated s.c. with 10 µg/kg/d estradiol via osmotic minipump. Estradiol treatment reduced testis, prostate weights, and serum androgen concentrations ( P < 0.05). Soy protein isolate had no effect. Estradiol up-regulated 489 and down-regulated 1237 testicular genes >1.5-fold ( P < 0.05). In contrast, soy protein isolate only significantly up-regulated expression of 162 genes and down-regulated 16 genes. The top 30 soy protein isolate-up-regulated genes shared 93% concordance with estradiol up-regulated genes. There was little overlap between soy protein isolate down-regulated genes and those down-regulated by estradiol treatment. Functional annotation analysis revealed significant differences in testicular biological processes affected by estradiol or soy protein isolate. Estradiol had major actions on genes involved in reproductive processes including down-regulation of testicular steroid synthesis and expression of steroid receptor activated receptor (Star) and cytochrome P450 17α-hydroxylase/(Cyp17a1). In contrast, soy protein isolate primarily affected pathways associated with macromolecule modifications including ubiquitination and histone methylation. Our results indicate that rather than acting as a weak estrogen in the developing testis, soy protein isolate appears to act as a selective estrogen receptor modulator with little effect on reproductive processes. Impact statement Soy protein isolate (SPI) is the sole protein used to make soy-based infant formulas. SPI contains phytoestrogens, which are structurally similar to estradiol. These phytoestrogens, daidzein, genistein, and equol, fit the definition of endocrine-disrupting compounds, and at high concentrations, have estrogenic actions resulting in reproductive toxicity in the developing male, when provided as isolated chemicals. However, few animal studies have examined the potential estrogenicity of SPI as opposed to pure isoflavones. In this study, SPI feeding did not elicit an estrogenic response in the testis nor any adverse outcomes including reduced testicular growth, or androgen production during early development in rats when compared to those receiving estradiol. These findings are consistent with emerging data showing no differences in reproductive development in males and female children that received breast milk, cow's milk formula, or soy infant formula during the postnatal feeding period.

Project description:BackgroundStudies show that by 3 months, over half of US infants receive formula, and guidelines play a key role in formula feeding. The question then is, what might happen if caregivers follow guidelines and, more specifically, are there situations where following guidelines can result in infants who are overweight/have obesity?MethodsWe used our "Virtual Infant" agent-based model representing infant-caregiver pairs that allowed caregivers to feed infants each day according to guidelines put forth by Johns Hopkins Medicine (JHM), Children's Hospital of Philadelphia (CHOP), Children's Hospital of the King's Daughters (CHKD), and Women, Infants, and Children (WIC). The model simulated the resulting development of the infants from birth to 6 months. The two sets of guidelines vary in their recommendations, and do not provide studies that support amounts at given ages.ResultsSimulations identified several scenarios where caregivers followed JHM/CHOP/CHKD and WIC guidelines, but infants still became overweight/with obesity by 6 months. For JHM/CHOP/CHKD guidelines, this occurred even when caregivers adjusted feeding based on infant's weight. For WIC guidelines, when caregivers adjusted formula amounts, infants maintained healthy weight.ConclusionsWIC guidelines may be a good starting point for caregivers who adjust as their infant grows, but the minimum amounts for JHM/CHKD/CHOP recommendations may be too high.ImpactOur virtual infant simulation study answers the question: can caregivers follow current formula-feeding guidelines and still end up with an infant who is overweight or has obesity? Our study identified several situations in which unhealthy weight gain and/or weight loss could result from following established formula-feeding recommendations. Our study also suggests that the minimum recommended amount of daily formula feeding should be lower for JHM/CHOP/CHKD guidelines to give caregivers more flexibility in adjusting daily feeding levels in response to infant weight. WIC guidelines may be a good starting point for caregivers who adjust as their infant grows. In order to understand how to adjust guidelines, we can use computational simulation models, which serve as "virtual laboratories" to help overcome the logistical and ethical issues of clinical trials.

Project description:Study questionIs soy formula feeding during infancy associated with menstrual pain in reproductive-age women?Summary answerOur data suggest that soy formula feeding during infancy is associated with several indicators of severe menstrual pain in reproductive-age women.What is known alreadyA prior study observed greater severity of menstrual pain in young women who as infants participated in feeding studies and were assigned to soy-based formula feeding.Study design, size, durationWe used data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1696 African-American women ages 23-35 years at enrollment.Participants/materials, settings, methodsData on infant soy formula feeding was ascertained by self-administered questionnaire for 1553 participants, with 89% of participants receiving assistance from their mothers. Information on menstrual pain indicators was collected by web- and telephone-interview. We estimated the relative risk (RR) and 95% confidence interval (CI) using log-binomial regression, or log-multinomial regression, adjusting for participant age and maternal education.Main results and the role of chanceWomen ever fed soy formula as infants were more likely than unexposed women to report ever use of hormonal contraception for menstrual pain (RR 1.4, CI: 1.1-1.9) and moderate/severe menstrual discomfort/pain with 'most periods', but not 'every period', during early adulthood (ages 18-22 when not using hormonal contraception) (RR 1.5, CI: 1.1-2.0).Limitations, reasons for cautionWe relied on retrospective recall to ascertain infant exposure to soy formula feeding and data on menstrual pain indicators.Wider implications of the findingsOur observations add to the growing body of literature from animal and human studies on the reproductive health consequences of early-life exposure to soy formula.Study funding/competing interest(s)This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences and, in part, by funds allocated for health research by the American Recovery and Reinvestment Act. This research was also supported by grant K99NR017191 (KU). None of the authors has a conflict of interest.Trial registration numberNot applicable.

Dataset Information

Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study.

Publications

Soy Formula Is Not Estrogenic and Does Not Result in Reproductive Toxicity in Male Piglets: Results from a Controlled Feeding Study.

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