Genistein exposure during the early postnatal period favors the development of obesity in female, but not male rats

• Published in: Toxicological sciences Vol. 138; no. 1; pp. 161 - 174
• Main Authors: Strakovsky, Rita S, Lezmi, Stéphane, Flaws, Jodi A, Schantz, Susan L, Pan, Yuan-Xiang, Helferich, William G
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.03.2014
• Subjects: Adiposity - drug effects; Administration, Oral; Animals; Animals, Newborn; Body Composition; CCAAT-Enhancer-Binding Protein-alpha - biosynthesis; CCAAT-Enhancer-Binding Protein-beta - biosynthesis; Female; Genistein - toxicity; Male; Obesity - chemically induced; Obesity - metabolism; Phytoestrogens - toxicity; Rats; Rats, Sprague-Dawley; Sex Characteristics; Wnt Proteins - biosynthesis; body composition; adipogenesis; genistein; methylation; obesity; soy infant formula
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kft331

Genistein (Gen), the primary isoflavone in soy, has been shown to adversely affect various endocrine-mediated endpoints in rodents and humans. Soy formula intake by human infants has been associated with early age at menarche and decreased female-typical behavior in girls. Adipose deposition and expansion are also hormonally regulated and Gen has been shown to alter these processes. However, little is known about the impact of early-life soy intake on metabolic homeostasis in adulthood. The current study examined the impact of early-life Gen exposure on adulthood body composition (by magnetic resonance imaging) and the molecular signals mediating adipose expansion. From postnatal day (PND) 1 to 22, rat pups were daily orally dosed with 50mg/kg Gen to mimic blood Gen levels in human infants fed soy formula. Female but not male Gen-exposed rats had increased fat/lean mass ratio, fat mass, adipocyte size and number, and decreased muscle fiber perimeter. PND22 Gen-exposed females, but not males, had increased expression of adipogenic factors, including CCAAT/enhancer binding protein alpha (Cebpα), CCAAT/enhancer binding protein beta (Cebpβ), and peroxisome proliferator-activated receptor gamma (Pparγ). Furthermore, Wingless-related MMTV integration site 10b (Wnt10b), a critical regulator of adipogenic cell fate determination, was hypermethylated and had decreased expression in adipose of PND22 Gen-exposed females. These data suggest that developmental Gen exposure in rats has gender-specific effects on adiposity that closely parallel the effects of a postweaning high-fat diet and underscore the importance of considering timing of exposure and gender when establishing safety recommendations for early-life dietary Gen intake.