Embryonic exposure to the fungicide vinclozolin causes virilization of females and alteration of progesterone receptor expression in vivo: an experimental study in mice

BACKGROUND: Vinclozolin is a fungicide that has been reported to have anti-androgenic effects in rats. We have found that in utero exposure to natural or synthetic progesterones can induce hypospadias in mice, and that the synthetic progesterone medroxyprogesterone acetate (MPA) feminizes male and virilizes female genital tubercles. In the current work, we selected a relatively low dose of vinclozolin to examine its in utero effects on the development of the genital tubercle, both at the morphological and molecular levels. METHODS: We gave pregnant dams vinclozolin by oral gavage from gestational days 13 through 17. We assessed the fetal genital tubercles from exposed fetuses at E19 to determine location of the urethral opening. After determination of gonadal sex, either genital tubercles were harvested for mRNA quantitation, or urethras were injected with a plastic resin for casting. We analyzed quantified mRNA levels between treated and untreated animals for mRNA levels of estrogen receptors α and β, progesterone receptor, and androgen receptor using nonparametric tests or ANOVA. To determine effects on urethral length (males have long urethras compared to females), we measured the lengths of the casts and performed ANOVA analysis on these data. RESULTS: Our morphological results indicated that vinclozolin has morphological effects similar to those of MPA, feminizing males (hypospadias) and masculinizing females (longer urethras). Because these results reflected our MPA results, we investigated the effects of in utero vinclozolin exposure on the mRNA expression levels of androgen, estrogen α and β, and progesterone receptors. At the molecular level, vinclozolin down-regulated estrogen receptor α mRNA in females and up-regulated progesterone receptor mRNA. Vinclozolin-exposed males exhibited up-regulated estrogen receptor α and progesterone receptor mRNA, effects we have also seen with exposure to the synthetic estrogen, ethinyl estradiol. CONCLUSION: The results suggest that vinclozolin virilizes females and directly or indirectly affects progesterone receptor expression. It also affects estrogen receptor expression in a sex-based manner. We found no in vivo effect of vinclozolin on androgen receptor expression. We propose that vinclozolin, which has been designated an anti-androgen, may also exert its effects by involving additional steroid-signaling pathways

Satellite observations for detecting and forecasting sea-ice conditions: A summary of advances made in the SPICES Project by the EU's Horizon 2020 Programme

The detection, monitoring, and forecasting of sea-ice conditions, including their extremes, is very important for ship navigation and offshore activities, and for monitoring of sea-ice processes and trends. We summarize here recent advances in the monitoring of sea-ice conditions and their extremes from satellite data as well as the development of sea-ice seasonal forecasting capabilities. Our results are the outcome of the three-year (2015-2018) SPICES (Space-borne Observations for Detecting and Forecasting Sea-Ice Cover Extremes) project funded by the EU's Horizon 2020 programme. New SPICES sea-ice products include pancake ice thickness and degree of ice ridging based on synthetic aperture radar imagery, Arctic sea-ice volume and export derived from multisensor satellite data, and melt pond fraction and sea-ice concentration using Soil Moisture and Ocean Salinity (SMOS) radiometer data. Forecasts of July sea-ice conditions from initial conditions in May showed substantial improvement in some Arctic regions after adding sea-ice thickness (SIT) data to the model initialization. The SIT initialization also improved seasonal forecasts for years with extremely low summer sea-ice extent. New SPICES sea-ice products have a demonstrable level of maturity, and with a reasonable amount of further work they can be integrated into various operational sea-ice services