A novel amphibian tier 2 testing protocol: a 30-week exposure of Xenopus tropicalis to the antiandrogen flutamide.

In 1996, the U.S. Congress mandated the development of a screening program for endocrine-disrupting chemicals (EDCs) using validated test systems. Subsequently, the Endocrine Disruptor Screening and Testing Advisory Committee recommended the development of a standardized amphibian assay for tier 2 testing of EDCs. For that reason, a tier 2 testing protocol using Xenopus (Silurana) tropicalis and a 30-week, flow-through exposure to the antiandrogen flutamide from stage 46 tadpoles through sexually mature adult frogs were developed and evaluated in this pilot study. The endpoints for this study included measurements of frog body lengths and weights, liver weights, ovary/egg mass weights, testicular and ovarian histopathology, plasma vitellogenin levels, and notes on any abnormalities observed at necropsy. Increasing exposure concentrations to flutamide caused significant increases in frogs with no recognizable gonadal tissue and increased body and liver weights in male frogs, whereas the body lengths and weights decreased significantly in female frogs. Important issues must be resolved before a tier 2 amphibian assay can be further developed and validated, including the establishment of baseline values in the controls for the parameters under study; the maintenance, measurement, and timing of exposure concentrations; and the development of additional biomolecular markers of effect. This study demonstrated the feasibility of conducting long-term EDC exposure studies using X. tropicalis.

Relationship between sperm characteristics and hormonal parameters in normal couples.

OBJECTIVE: To examine the relationships between hormone profiles and semen analysis measures and fertility in the male partners of presumed normal couples. DESIGN: Prospective clinical study. SETTINGS: Healthy volunteers in an academic research environment. PATIENT(S): One hundred forty-five reproductive age couples without known risk factors for infertility and who had discontinued contraception to achieve pregnancy completed this component of this study. Each couple was followed for < or =12 menstrual cycles while they attempted to conceive. INTERVENTION(S): Semen quality measures for the first ejaculates were obtained at the start of the study along with a single blood sample. Levels of FSH, bioactive FSH, inhibin B, LH, and T were measured for each man. MAIN OUTCOME MEASURE(S): Semen analysis, FSH, inhibin B, LH, T, and clinical pregnancy. RESULTS: Significant positive relationships were observed between the two measures of FSH as well as between both of the FSH measures and LH. Follicle-stimulating hormone as measured by RIA was significantly negatively correlated with inhibin B. Inhibin B showed a marginally significant negative correlation with LH, and LH and T had a marginally significant positive correlation. Inhibin B increased significantly, and both measures of FSH activity showed significant decreases, with increasing levels in several semen quality measures. There was no significant relationship between the measured hormones and the pregnant and nonpregnant groups or time to pregnancy. CONCLUSION(S): These results contribute additional information on the utility of reproductive hormone measurements for predicting semen quality in couples without known reduced fertility.