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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #346397
Title: Soy protein isolate feeding does not result in reproductive toxicity in the pre-pubertal rat testis

Author
item RONIS, MARTIN - Louisiana State University
item GOMEZ-ACEBEDO, HORACIO - University Of Arkansas
item SHANKAR, KARTIK - University Of Arkansas
item SHARMA, NEHA - Arkansas Children'S Nutrition Research Center (ACNC)
item BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC)
item SINGHAL, ROHIT - Arkansas Children'S Nutrition Research Center (ACNC)
item MERCER, KELLY - University Of Arkansas
item Badger, Thomas

Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/9/2018
Publication Date: 5/1/2018
Citation: Ronis, M.J., Gomez-Acebedo, H., Shankar, K., Sharma, N., Blackburn, M., Singhal, R., Mercer, K.E., Badger, T.M. 2018. Soy protein isolate feeding does not result in reproductive toxicity in the pre-pubertal rat testis. Experimental Biology and Medicine. 243:695-707. https://doi.org/10.1177/1535370218771333.
DOI: https://doi.org/10.1177/1535370218771333

Interpretive Summary: Soy protein isolate (SPI), the sole protein source in soy infant formulas, contains phytoestrogens, i.e. genistein and diadzein. There are concerns that exposure to these phytoestrogens during the first year of life may have adverse effects on the developing male reproductive tract. To evaluate the impact of SPI on male testes, young male rats were fed diets containing either casein protein or soy protein, and compared to age-matched males fed the casein or soy protein diets supplemented with estradiol(an estrogen hormone used as a positive experimental treatment). Estrogen exposure during this period is known to reduce male testis size and disrupt male reproductive development. As expected, estradiol supplementation reduced testis size and circulating testosterone levels, suggestive of reproductive toxicity. Males receiving soy diets alone had normal testis weight, normal testosterone blood concentrations and normal reproductive development. Combining the soy protein diet with estradiol supplementation in young male rats showed that active components in soy protein are actually anti-estrogenic. These findings show that soy protein used in infant formulas is not toxic in a rodent model of male reproductive health.

Technical Abstract: 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 mg/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 downregulated 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 upregulated 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 17a-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.