Polybrominated diphenyl ethers (PBDEs) were used as flame-retardant additives starting 1965 and were recently withdrawn from commerce in North America and Europe. Approximately 1/5 of the total U.S. population were born when environmental concentrations of PBDE plateaued at their maximum. Accumulating evidence suggests that developmental exposures to PBDE may result in long-lasting programming of liver metabolism. In this study, CD-1 mice were exposed prenatally or neonatally to 1 mg/kg body weight of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), and changes in liver histology, transcriptome, and liver-blood balance of triglycerides were analyzed in 10 months old male offspring. In both exposure groups, long-term reprogramming of lipid metabolism was observed, including increased liver triglycerides and decreased blood triglycerides, and altered expression of metabolic genes in the liver. Significant upregulation of lipid influx transporter Cd36 2.3- and 5.7-fold in pre- and neonatal exposure groups, respectively was identified as a potential mechanism of blood/liver imbalance of triglycerides. Analysis of our and previously published all-genome gene expression data identified changes in expression of ribosomal protein genes as a transcriptomic signature of PBDE exposure. Further comparison of our new data and published data demonstrate that low doses (0.2 mg/kg body weight) of PBDE induce long-lasting up-regulation of ribosomal genes, suppression of Cd36 in liver and increase circulating triglycerides in blood, while moderated doses (≥1 mg/kg body weight) produce opposite long-lasting effects. To conclude, this study shows that an environmentally relevant developmental exposures to BDE-47 permanently alter lipid uptake and accumulation in the liver, with low and moderate doses having opposite effect on liver transcriptomics and triglyceride balance. Similar effects of pre- and neonatal exposures point at hepatocyte maturation as a sensitive window of the liver metabolism programming. These results suggest that PBDE exposure may be an important factor increasing risks of cardio-vascular disease and non-alcoholic fatty liver disease via modulation of liver/blood balance of lipids. The translational relevance of these findings for human remain to be studied.
Resumen. En muchas aves paseriformes, las tasas de paternidad extra-pareja son altas, pero pocos estudios han examinado los comportamientos que usan las hembras para obtener cópulas extra-pareja. Estudiamos el comportamiento extra-pareja en hembras de Empidonax virescens, una especie en la cual el 58% de las hembras produce pichones extra-pareja y en que los machos frecuentemente engendran crías en territorios distantes. Seguimos a las hembras utilizando radio telemetría para documentar el alcance y la frecuencia de las salidas de sus territorios. Además empleamos observaciones de comportamiento y experimentos con reproducción de llamadas previamente grabadas para evaluar si las vocalizaciones de las hembras publicitan su fertilidad. Ninguna de las hembras marcadas con transmisores dejaron sus territorios (n = 12 hembras, 105 hs de seguimiento) incluso durante la hora antes del amanecer. Los análisis de paternidad revelaron que al menos seis de estas hembras produjeron pichones al extra-pareja. Observaciones focales revelaron que las hembras fértiles gastaron significativamente más tiempo realizando llamados tipo "chiff," emitieron más llamadas por hora y solicitaron más encuentros que las hembras que incubaban. El alcance del llamado "chiff" de las hembras durante sus períodos de fertilidad no se relacionó con una subsecuente paternidad extra-pareja en sus nidos (n = 12). Evaluamos si el llamado "chiff" tiene una función de defensa del territorio mediante la reproducción de llamados a hembras en etapas fértiles y de incubación. Las hembras en sus territorios respondieron a las grabaciones acercándose o volando sobre el parlante, no aumentaron significativamente sus tasas de llamados "chiff," pero si emitieron otras llamadas de alta intensidad. Nuestros resultados sugieren que las fertilizaciones extra-pareja en E. virescens se dan primariamente en el propio territorio de una hembra y que los machos extra-pareja podrían usar las vocalizaciones de las hembras para localizar a las hembras fértiles.Abstract. In many passerines, rates of extra-pair paternity are high, but relatively few studies have examined the behaviors females use to obtain extra-pair copulations. We studied extra-pair behavior in females of the Acadian flycatcher (Empidonax virescens), a species in which 58% of females produce extra-pair young and males often sire offspring on distant territories. We used radiotelemetry to document the extent and frequency of females' forays away from their territories and used behavioral observations and playback experiments to test if females' vocalizations advertise their fertility. No radio-tagged females left their territories (n = 12 females, 105 hr of tracking) even during the hour before dawn. Paternity analyses revealed that at least six of these females produced extrapair young. focal observations revealed that fertile females spent significantly more time calling "chiff," gave more calls per hour, and called in longer bouts than did incubating females. Extent of females' chiffing during their fertile p...
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