Soy formula is not estrogenic and does not result in reproductive toxicity in male piglets: Results from a controlled feeding study

Authors: RONIS, MARTIN JJ - Louisiana State University; GOMEZ-ACEVEDO, HORACIO - University Arkansas For Medical Sciences (UAMS); SHANKAR, KARTIK - University Of Colorado; HENNINGS, LEAH - University Arkansas For Medical Sciences (UAMS); SHARMA, NEHA - Arkansas Children'S Nutrition Research Center (ACNC); BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC); MIOUSEE, ISABELLE - University Arkansas For Medical Sciences (UAMS); Dawson, Harry; Chen, Celine; MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC); Badger, Thomas

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/27/2022
Publication Date: 3/7/2022
Citation: Ronis, M., Gomez-Acevedo, H., Shankar, K., Hennings, L., Sharma, N., Blackburn, M.L., Miousee, I., Dawson, H.D., Chen, C.T., Mercer, K.E., Badger, T.M. 2022. Soy formula is not estrogenic and does not result in reproductive toxicity in male piglets: Results from a controlled feeding study. Nutrients. 14(5):1126. https://doi.org/10.3390/nu14051126.
DOI: https://doi.org/10.3390/nu14051126

Interpretive Summary: Soy-based baby formula has risen concerns for possibly affecting reproduction later in life. These concerns are based on the presence of substances (estrogens) found in soy products. This paper compare the effects on testis of newborn piglets fed with soy formula, cow's milk, and a combination of milk and two estrogens (estradiol and genistein). We found that soy formula is not toxic in the pigs testis development. Since pig testis development is very similar to humans, we concluded that soy is safe to consume by infant boys.

Technical 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) 25 from postnatal day 2 until day 21. E2 treatment reduced testis weight (P<0.05) as % body weight; significantly suppressed serum androgen concentrations, increased tubule area, Germ cell and Sertoli cell numbers (P<0.05) relative to 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.