title: Comparative evaluation of the teratogenicity of genistein and genistin using rat whole embryo culture and limbud micromass culture methods.
abstract: Genistein (GEN) is one kind of phytoestrogen. Several studies have demonstrated the teratogenic potential of GEN in vitro by postimplantation rat whole embryo culture (WEC) assay, but GEN showed no teratogenic effects in vivo even at a dose up to 1000 mg/kg bw/day. The mechanism of such discrepancy is still unclear. Because more than 80% of total genistein (free plus glycoside form) in circulation is its glycoside metabolite, genistin (GIN), we thus hypothesize that genistin is non-teratogenic. To prove this hypothesis, rat whole embryo culture (WEC) and limbud micromass culture methods were applied to compare the teratogenic effects of GEN and GIN on developing embryos in vitro. In WEC assay, we found that the development of embryos was affected by GEN treatment dose-dependently, while GIN-treated embryos displayed slight developmental defects only at the highest dose (222 μM). In micromass culture assay, the IC50 of cell proliferation and differentiation for GEN were 15.6 and 37.2 μM, respectively, while neither was influenced by GIN treatment up to 111 μM. Collectively, our study indicated that GEN showed no teratogenic effects in vivo probably due to its transformation to the non-teratogenic metabolite, GIN.
authors.affiliation: Department of Toxicology, School of Public Health, Peking University, Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zou
authors.forename: Lina
authors.initials: L
authors.lastname: Xing
authors.forename: Qiuqiong
authors.initials: Q
authors.lastname: Tang
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Weidong
authors.initials: W
authors.lastname: Hao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects*; D005121:Extremities / Q000196:embryology*; D005260:Female; D019833:Genistein / Q000633:toxicity*; D020128:Inhibitory Concentration 50; D007529:Isoflavones / Q000633:toxicity*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*
chemical_list: D007529:Isoflavones; D013723:Teratogens; C040641:genistin; D019833:Genistein