Male testicular development is affected by estrogens but not altered in neonatal piglets receiving soy infant formula

Abstract

Soy infant formula contains many phytochemicals, including phytoestrogens, which are structurally similar to estradiol (E2). As a result of their potentially estrogenic properties, soy infant formulas have been the subject of concern with regards to reproductive toxicity. To address these concerns regarding male reproductive development, we fed male piglets a soy‐based infant formula, a dairy milk‐based infant formula, milk formula supplemented with E2, or milk formula supplemented with putative estrogenic soy phytonutrient genistein (GEN), in comparison with piglets receiving sow's breast milk from postnatal day 2–21. In the E2 supplemented group, serum testosterone and testicular weight were significantly reduced compared to the milk formula‐fed and sow's milk controls. Testis tubule area, Sertoli cell and germ cell numbers were also increased in the E2 supplemented group compared to milk formula controls, P<0.05. When compared to the sow's milk control, RNAseq analysis in testes showed that E2 supplemented milk formula altered expression of 2012 testicular genes (±1.5 fold, P<0.100). Functional annotation analysis indicated up‐regulation of several pathways in the E2 supplemented group, including canonical Wnt signaling, cell differentiation and migration, angiogenesis and spermatogenesis. E2 also down‐regulated cholesterol and androgen synthesis pathways. Real‐time RT‐PCR confirmed the decrease in steroidogenic acute regulatory protein (Star) mRNA in the E2 supplemented group, suggesting a potential mechanism for the observed decrease in serum testosterone in this diet group. In contrast, GEN supplementation of milk formula altered 104 genes, soy formula 49 genes, and the pathways impacted had no clear links to testes function or sex organ development. These data show that early infant diet exposure to phytoestrogens in soy‐based infant formula are not estrogenic in the male reproductive system.Support or Funding InformationThis work was funded by USDA‐ARS Project 6026‐5100‐010‐05S.