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

Purpose 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. Materials and Methods Fetal domestic swine and miniswine were injected with 1 micro g./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 alpha 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 alpha 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 alpha protein expression in testis appeared to be increased by dioxin exposure. Aberrant regulation of estrogen receptor alpha expression by dioxin may contribute to reproductive tract anomalies in male fetuses.