title: Effects of an environmental endocrine disruptor on fetal development, estrogen receptor(alpha) and epidermal growth factor receptor expression in the porcine male genital tract.
abstract: OBJECTIVE
  We studied the effect of a potent reproductive tract toxin, 2,3,7,8-tetrachlorodibenzo-rho-dioxin, on fetal development and expression of estrogen receptor alpha and epidermal growth factor receptor (EGFR) in male swine.
  
  
  METHODS
  Fetal domestic swine and miniswine were injected with 1 microg./kg. dioxin on day 50 of gestation and removed near term (114 days). Germ cell counts were performed on sections of formalin fixed testes. Estrogen receptor a protein, and messenger ribonucleic acid (mRNA) and EGFR mRNA expression were analyzed in frozen tissue using Western blotting and semiquantitative reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  Of 15 dioxin exposed male offspring 8 (53%) had genital anomalies, including cryptorchidism in 4, epididymal detachment in 1, epididymal atresia in 1 and vasal dilatation in 3, while 3 of 17 control male swine (18%) had incompletely descended testes (p = 0.06). High intra-abdominal testes were found in 3 of 4 cryptorchid dioxin exposed but no control male swine. Mean germ cell number per tubule was 4.0+/-1.1 and 2.7+/-0.7 in control and dioxin groups, respectively (p = 0.01). Estrogen receptor a protein and mRNA were identified in fetal uterus, testis, gubernaculum and epididymis. Protein levels were 2 to 3-fold higher in dioxin exposed testis, and mRNA levels were significantly lower in gubernaculum and epididymis. EGFR mRNA expression was similar in treated and control testis and epididymis.
  
  
  CONCLUSIONS
  Preliminary data suggest that dioxin produces cryptorchidism and wolffian duct anomalies in male swine exposed just before mid gestation. Germ cell counts and estrogen receptor alpha mRNA expression in gubernaculum and epididymis were significantly reduced, and estrogen receptor a protein expression in testis appeared to be increased by dioxin exposure. Aberrant regulation of estrogen receptor a expression by dioxin may contribute to reproductive tract anomalies in male fetuses.
authors.affiliation: Department of Urology, Children's Hospital of Michigan and Wayne State University School of Medicine, Detroit, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Barthold
authors.forename: J V
authors.initials: JV
authors.lastname: Kryger
authors.forename: A M
authors.initials: AM
authors.lastname: Derusha
authors.forename: B P
authors.initials: BP
authors.lastname: Duel
authors.forename: R
authors.initials: R
authors.lastname: Jednak
authors.forename: D F
authors.initials: DF
authors.lastname: Skafar
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics; D047628:Estrogen Receptor alpha; D005837:Genitalia, Male / Q000187:drug effects* / Q000254:growth & development*; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics; D013552:Swine
chemical_list: D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D066246:ErbB Receptors