Učinci prenatalne i postnatalne izloženosti perfluorooktanskoj kiselini na ekspresiju glavnih gena povezanih s reprodukcijom u mišjem hipotalamusu i spolnim žlijezdama

Perfluorooctanoic acid (PFOA), a ubiquitous environmental pollutant reported to be an endocrine disruptor, is used in many industrial and consumer products. Although the adverse effects of PFOA on the reproductive health of animals and humans have been widely reported, most studies have focused on assessing the anatomical features and conventional histology of adult gonads. Therefore, the molecular mechanisms activated in the hypothalamus and gonads following PFOA exposure during the pre- and postnatal periods are not clear. This study used a mouse model to evaluate the effects of PFOA exposure on the alteration of molecular mechanisms in the hypothalamus and gonads during the prenatal and postpartum periods. Changes in gene and protein expression following PFOA exposure were evaluated by quantitative polymerase chain reaction and Western blotting, respectively. Kisspeptin 1 and gonadotropin-releasing hormone expression in the hypothalamus of female and male mouse pups was significantly decreased. Additionally, Cyp17a1 expression was upregulated in male offspring testes, while Cyp17a1 and Cyp19a1 expression was downregulated in female offspring ovaries. Changes at the molecular level due to PFOA exposure in the early stages of development did not show sex-related differences in the hypothalamus; however, such differences were confirmed in the gonads. These results could be used as basic data to study the molecular mechanisms underlying the reproductive dysfunction caused by PFOA exposure in the early stages of embryonic development.Perfluorooktanska kiselina (PFOA) sveprisutna je onečišćujuća tvar za okoliš, za koju je zabilježeno da uzrokuje i endokrinopatije, a upotrebljava se u mnogim industrijskim proizvodima. Bez obzira na poznate i zabilježene nuspojave PFOA-e na reproduktivno zdravlje životinja i ljudi, većina se istraživanja usredotočuje na procjenu anatomskih histoloških značajki u spolnim žlijezdama odraslih jedinki. Molekularni mehanizmi koji se aktiviraju u hipotalamusu i spolnim žlijezdama nakon izlaganja PFOA-i stoga nisu razjašnjeni. U ovom je istraživanju upotrijebljen mišji model za procjenu učinaka izlaganja PFOA-i na promjenu molekularnih mehanizama u hipotalamusu i spolnim žlijezdama za vrijeme prijeporođajnog i poslijeporođajnog razdoblja. Promjene u ekspresiji gena i proteina nakon izloženosti PFOA-i analizirane su kvantitativnom PCR metodom i metodom Western blotting. Ekspresija kispeptina 1 i hormona koji oslobađa gonadotropin u hipotalamusu ženske i muške mladunčadi bila je znakovito smanjena. Osim toga ekpresija Cyp17a1 bila je pojačana u testisima muških potomaka, dok je ekspresija Cyp17a1 i Cyp19a1 u jajnicima ženskih potomaka bila smanjena. Kod promjena na molekularnoj razini u hipotalamusu u ranim razvojnim stadijima nije bilo razlike među spolovima, dok je kod promjena u spolnim žlijezdama povrđena razlika među spolovima. Rezultati ovog istraživanja mogli bi biti korisni kao osnovni podaci u proučavanju molekularnih mehanizama podležeće reproduktivne disfunkcije uzrokovane izloženošću PFOA-i u ranim stadijima embrionalnog razvoja

Ductile Fracture Simulation of Full-scale Circumferential Cracked Pipes: (II) Stainless Steel

AbstractThis paper reports ductile fracture simulation of full-scale circumferentially cracked pipes using finite element (FE) damage analysis. In the structural integrity, without experimental investigations or with few ones, it is not an easy task to properly evaluate the crack initiation and crack propagation of large-scale components with a crack-like defect. Unfortunately, from an economic perspective, performing experiments of large-scale components would be consequently unfavorable. For these reasons, ductile fracture simulation using FE damage analysis to predict crack behavior is one efficient way to replace the test procedures. In order to simulate ductile tearing of large-scale cracked pipes, element-size-dependent critical damage model based on the stress-modified fracture strain model is proposed. To evaluate fracture behavior of full-scale cracked pipes, tensile and C(T) specimens are calibrated by FE analysis technique. Tensile properties and fracture toughness of stainless steel at 288oC are taken from Battelle Pipe Fracture Encyclopedia. After calibrations, simulated results of the full-scale pipes with a circumferential crack are compared with test data to validate the proposed method

Exposures to Particulate Matter and Polycyclic Aromatic Hydrocarbons and Oxidative Stress in Schoolchildren

BACKGROUND: Air pollution is known to contribute to respiratory and cardiovascular mortality, and morbidity. Oxidative stress has been suggested as one of the main mechanisms for these effects on health. OBJECTIVE: The aim of this study was to analyze the effects of exposure to particulate matter (PM) with aerodynamic diameters <= 10 mu m (PM(10)) and <= 2.5 mu M (PM(2.5)) and polycyclic aromatic hydrocarbons (PAHs) on urinary malondialdehyde (MDA) levels in schoolchildren. METHODS: The study population consisted of 120 schoolchildren. The survey and measurements were conducted in four cities two in China (Ala Shan and Beijing) and two in Korea (Jeju and Seoul) between 4 and 9 June 2007. We measured daily ambient levels of PM and their metal components at the selected schools during the study period. We also measured urinary 1-hydroxypyrene (1-OHP) and 2-naphthol, to assess PAH exposure, and MDA, to assess oxidative stress. Measurements were conducted once a day for 5 consecutive days. We constructed a linear mixed model after adjusting for individual variables to estimate the effects of PM and PAH on oxidative stress. RESULTS: We found statistically significant increases in urinary MDA levels with ambient PM concentrations from the current day to the 2 previous days (p < 0.0001). Urinary 1-OHP level also showed a positive association with urinary MDA level, which was statistically significant with or without PM in the model (p < 0.05). Outdoor PM and urinary 1-OHP were synergistically associated with urinary MDA levels. Some metals bound to PM(10) (aluminum, iron, strontium, magnesium, silicon, arsenic, barium, zinc, copper, and cadmium) and PM(2.5) (magnesium, iron, strontium, arsenic, cadmium, zinc, aluminum, mercury, barium, and copper) also had significant associations with urinary MDA level. CONCLUSION: Exposure to PM air pollution and PAHs was associated with oxidative stress in schoolchildren.Environmental SciencesPublic, Environmental & Occupational HealthToxicologySCI(E)40ARTICLE4579-58311

Epigenetic toxicity and cytotoxicity of perfluorooctanoic acid and its effects on gene expression in embryonic mouse hypothalamus cells

Premda je perfluorooktanska kiselina (PFOA) dobro znana kao endokrini disruptor, i dalje se malo zna o mehanizmima u pozadini njezina djelovanja na stanice i njezine toksičnosti u kritičnoj fazi razvoja hipotalamusa. Stoga smo istražili njezino djelovanje u staničnoj liniji N46 hipotalamusa mišjeg embrija (mHypoE-N46) da bismo saznali o mehanizmima kroz koje ih PFOA oštećuje. S tom smo svrhom analizirali vijabilnost stanica, globalnu metilaciju DNA i gensku ekspresiju izloženih stanica. Porastom koncentracija PFOA padala je stanična vijabilnost, a globalna DNA metilacija rasla. Usto je PFOA značajno utjecala na ekspresiju gena povezanih s apoptozom i staničnim ciklusom, neurotrofnih gena te Tet, Dnmt i Mecp2 gena. Naše istraživanje ukazuje na to da izloženost PFOA utječe na preživljenje stanica hipotalamusa mišjeg embrija reprogramiranjem obrazaca metilacije DNA te promjenama u genima zaduženim za održavanje homeostaze. Metilacija DNA i promjene u ekspresiji Mecp2 gena izazvane djelovanjem PFOA također imaju široki spektar implikacija, budući da utječu na promjene u genima zaduženim za druge važne mehanizme u embrijskom hipotalamusu. Stoga naše istraživanje može poslužiti kao dobra polazna točka za daljnje istraživanje mehanizama djelovanja PFOA na razvoj hipotalamusa.Even though the endocrine-disrupting potential of perfluorooctanoic acid (PFOA) is well known, the mechanisms underlying its cellular and epigenetic toxicity at the critical stage of hypothalamic development are poorly understood. This is why we studied its effects on the embryonic mouse hypothalamic cell line N46 (mHypoE-N46) with a hope to shed more light on the mechanisms through which PFOA causes embryonic hypothalamic cell damage. To do that, we studied cell viability, global DNA methylation, and gene expression in cells exposed to PFOA. As the PFOA dose increased, cell viability decreased, while global DNA methylation increased. PFOA also significantly altered the expression of genes related to the apoptosis and cell cycle, neurotrophic genes, and the Tet, Dnmt, and Mecp2 genes. Our findings suggest that exposure to PFOA affects cell survival through the reprogramming of embryonic hypothalamic DNA methylation patterns and altering cell homeostasis genes. DNA methylation and changes in the Mecp2 gene expression induced by PFOA also imply wider ramifications, as they alter genes of other major mechanisms of the embryonic hypothalamus. Our study may therefore serve as a good starting point for further research into the mechanisms of PFOA effect of hypothalamic development