title: Acute and chronic effects of oral genistein administration in neonatal mice.
abstract: Soy-based infant formulas are widely used in the United States and some other countries. These formulas contain high levels of the estrogenic isoflavone genistein, leading to concern that neonatal genistein exposure could cause acute and/or long-term adverse effects on reproductive and other organs. However, previous work to assess genistein effects in rodent models has not typically replicated the route of delivery and/or serum genistein concentrations reported for soy formula-fed human infants. Our objective was to develop a mouse model that more closely mimics the oral genistein exposure and total serum genistein concentrations observed in soy formula-fed infants. Mouse pups were dosed orally with genistein in a soy formula-corn oil emulsion from Postnatal Day (PND) 1 to PND 5, then effects on reproductive and non-reproductive organs were assessed after dosing and during subsequent development. Neonatal treatment resulted in changes both at the completion of dosing (PND 5) and in adult animals. At PND 5, neonatal genistein treatment caused increased relative uterine weight and down-regulation of progesterone receptor in uterine epithelia. Estrogenic effects of genistein were also seen in the neonatal ovary and thymus, which had an increase in the incidence of multioocyte follicles (MOFs) and a decrease in thymic weight relative to body weight, respectively. The increased incidence of MOFs persisted into adulthood for neonatally treated genistein females, and estrous cycle abnormalities were seen at 6 mo of age despite normal fertility in these mice. The immediate and long-term effects in this neonatal animal model raise concerns that high serum concentrations of genistein are estrogenic and could potentially impact the development of human infants fed soy formula.
authors.affiliation: Department of Veterinary Biosciences, Division of Nutritional Sciences, University of Illinois, 2001 S. Lincoln Ave., Urbana, IL 61802, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Cimafranca
authors.forename: Juanmahel
authors.initials: J
authors.lastname: Davila
authors.forename: Gail C
authors.initials: GC
authors.lastname: Ekman
authors.forename: Rachel N
authors.initials: RN
authors.lastname: Andrews
authors.forename: Steven L
authors.initials: SL
authors.lastname: Neese
authors.forename: Jackye
authors.initials: J
authors.lastname: Peretz
authors.forename: Kellie A
authors.initials: KA
authors.lastname: Woodling
authors.forename: William G
authors.initials: WG
authors.lastname: Helferich
authors.forename: Jhimly
authors.initials: J
authors.lastname: Sarkar
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
authors.forename: Susan L
authors.initials: SL
authors.lastname: Schantz
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
authors.forename: Paul S
authors.initials: PS
authors.lastname: Cooke
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D003314:Corn Oil; D005260:Female; D019833:Genistein / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D005836:Genitalia, Female / Q000187:drug effects*; D006801:Humans; D007223:Infant; D041943:Infant Formula; D051379:Mice; D008810:Mice, Inbred C57BL; D048789:Phytoestrogens / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D048789:Phytoestrogens; D003314:Corn Oil; D019833:Genistein