Effects of an environmental endocrine disruptor on fetal development, estrogen receptor alpha and epidermal growth factor receptor expression in the porcine male genital tract

Purpose: We studied the effect of a potent reproductive tract toxin, 2,3,7, 8-tetrachlorodibenzo-rho-dioxin, on fetal development and expression of est rogen receptor alpha and epidermal growth factor receptor (EGFR) in male sw ine. Materials and Methods: Fetal domestic swine and miniswine were injected wit h 1 mu 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. Es trogen receptor alpha protein, and messenger ribonucleic acid (mRNA) and EG FR mRNA expression were analyzed in frozen tissue using Western blotting an d 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 atre sia 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 w ere found in 3 of 4 cryptorchid dioxin exposed but no control male swine. M ean 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 epididy mis. Protein levels were 2 to S-fold higher in dioxin exposed testis, and m RNA levels were significantly lower in gubernaculum and epididymis. EGFR mR NA expression was similar in treated and control testis and epididymis. Conclusions: Preliminary data suggest that dioxin produces cryptorchidism a nd wolffian duct anomalies in male swine exposed just before mid gestation. Germ cell counts and estrogen receptor alpha mRNA expression in gubernacul um and epididymis were significantly reduced, and estrogen receptor a prote in expression in testis appeared to be increased by dioxin exposure. Aberra nt regulation of estrogen receptor alpha expression by dioxin may contribut e to reproductive tract anomalies in male fetuses.