title: Permanent oviduct posteriorization after neonatal exposure to the phytoestrogen genistein.
abstract: BACKGROUND
  Preimplantation embryo loss during oviduct transit has been observed in adult mice after a 5-day neonatal exposure to the phytoestrogen genistein (Gen; 50 mg/kg/day).
  
  
  OBJECTIVE
  We investigated the mechanisms underlying the contribution of the oviduct to infertility.
  
  
  METHODS
  Female mice were treated on postnatal days 1-5 with corn oil or Gen (50 mg/kg/day). We compared morphology, gene expression, and protein expression in different regions of the reproductive tracts of Gen-treated mice with those of control littermates at several time points.
  
  
  RESULTS
  Neonatal Gen treatment resulted in substantial changes in expression of genes that modulate neonatal oviduct morphogenesis, including Hoxa (homeobox A cluster), Wnt (wingless-related MMTV integration site), and hedgehog signaling genes. An estrogen receptor antagonist blocked these effects, indicating that they were induced by the estrogenic activity of Gen. Oviducts of adults treated neonatally with Gen had abnormal morphology and were stably "posteriorized," as indicated by altered Hoxa gene patterning during the time of treatment and dramatic, permanent up-regulation of homeobox genes (e.g., Pitx1, Six1) normally expressed only in the cervix and vagina.
  
  
  CONCLUSIONS
  Neonatal exposure to estrogenic environmental chemicals permanently disrupts oviduct morphogenesis and adult gene expression patterns, and these changes likely contribute to the infertility phenotype.
authors.affiliation: Reproductive Medicine Group, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Jefferson
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Padilla-Banks
authors.forename: Jazma Y
authors.initials: JY
authors.lastname: Phelps
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Gerrish
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Williams
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D019833:Genistein / Q000494:pharmacology / Q000633:toxicity*; D015151:Immunoblotting; D007246:Infertility / Q000139:chemically induced* / Q000235:genetics; D051379:Mice; D046228:Microarray Analysis; D009024:Morphogenesis; D010057:Oviducts / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D048789:Phytoestrogens / Q000494:pharmacology / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D048789:Phytoestrogens; D014157:Transcription Factors; D019833:Genistein