Chronic Dietary Exposure to a Low-Dose Mixture of Genistein and Vinclozolin Modifies the Reproductive Axis, Testis Transcriptome, and Fertility

Background: The reproductive consequences and mechanisms of action of chronic exposure to low-dose endocrine disruptors are poorly understood.[br/] Objective: We assessed the effects of a continuous, low-dose exposure to a phytoestrogen (genistein) and/or an antiandrogenic food contaminant (vinclozolin) on the male reproductive tract and fertility.[br/] Methods: Male rats were exposed by gavage to genistein and vinclozolin from conception to adulthood, alone or in combination, at low doses (1 mg/kg/day) or higher doses (10 and 30 mg/kg/day). We studied a number of standard reproductive toxicology end points and also assessed testicular mRNA expression profiles using long-oligonucleotide microarrays.[br/] Results: The low-dose mixture and high-dose vinclozolin produced the most significant alterations in adults: decreased sperm counts, reduced sperm motion parameters, decreased litter sizes, and increased post implantation loss. Testicular mRNA expression profiles for these exposure conditions were strongly correlated. Functional clustering indicated that many of the genes induced belong to the “neuroactive ligand-receptor interactions” family encompassing several hormonally related actors (e.g., follicle-stimulating hormone and its receptor). All exposure conditions decreased the levels of mRNAs involved in ribosome function, indicating probable decreased protein production.[br/] Conclusions: Our study shows that chronic exposure to a mixture of a dose of a phytoestrogen equivalent to that in the human diet and a low dose—albeit not environmental—of a common anti-androgenic food contaminant may seriously affect the male reproductive tract and fertility

Comparative response of EPO and soluble transferrin receptor at high altitude

PURPOSE: Soluble transferrin receptor (sTfR) classically raises with increased erythropoiesis, along with the rise in erythropoietin (EPO). However, the specific effect of altitude-induced erythropoiesis on sTfR remains poorly documented. This study investigated the response of sTfR during high-altitude exposure in human and verified that sTfR was related to EPO response in this case. METHODS: EPO, sTfR, red cell volume (RCV), ferritin, and iron intake were measured during: 1) experiment A (N = 8, 31 d at 5000-8848 m), at sea level (SL), and at the simulated altitude of 5000, 6000, 7000, and 8000 m; and 2) during experiment B (N = 10, 7 d at 4350 m), at SL, after 3, 5, and 7 d at 4350 m and 1-2 d after return to SL (RSL). RESULTS: In experiment A, progressive decompression from SL to 8000 m induced a large parallel rise in EPO (33.8-fold) and sTfR (5.9-fold), whereas ferritin was dramatically decreased and iron intake reduced. RCV was increased after 31 d of decompression. In experiment B, EPO peaked at day 3 at 4350 m, then declined later at altitude and returned to baseline values at RSL, whereas sTfR progressively rose at altitude (+86%) and remained elevated during RSL (+64%). Ferritin progressively declined at 4350 m, whereas iron intake was unchanged. RCV was not enhanced after exposure to 4350 m. CONCLUSION: In summary, sTfR mirrors EPO response for a given level of altitude hypoxia but differs from EPO response during transitory phases, such as early acclimatization or reoxygenation. Analysis of sTfR may therefore account for altitude-related erythropoiesis, at a time when EPO is blunted

Comparison of fifteen immunoassays for the measurement of serum MUC-1/CA 15-3 in breast cancer patients

Peer Reviewe

The level of evidence for the use of biomarkers in the early detection of prostate cancer

International audienceTo systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review. We attributed a level of evidence (LoE) of IA to PSA for early PCa detection, but we do not recommend its use in mass screening. Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5); fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCa mortality. The LoE attributed was III-C. PSA can be used for early prostate cancer detection but mass screening is not recommended. Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed. A better use of available tests is possible for men at risk in order to maximize the risk-benefit ratio