Bisphenol S (BPS) is widely used to replace the known endocrine disruptor BPA in various products. We evaluated the effect of acute in vivo BPS exposure on oocyte quality, simulating the oral route of exposure via oral gavage. Eight-week-old ICR female mice (N = 15 per experimental group) were exposed to vehicle or BPS1-BPS4 (0.001, 0.1, 10, and 100 ng BPS x g bw-1 day-1, respectively) for seven days. Oocytes were isolated and matured in vitro. We observed that BPS exposure increased aberrant spindle formation in mature oocytes and induced DNA damage. Moreover, BPS3 significantly increased the chromatin repressive marks 5-methyl cytosine (5meC) and H3K27me2 in immature oocytes. In the BPS2 group, the increase in 5meC occurred during oocyte maturation. Transcriptome analysis revealed differential expression of early embryonic development transcripts in BPS2-exposed oocytes. These findings indicate that the biological effect of BPS is non-monotonic, affecting oocyte quality even at concentrations that are orders of magnitude below those measured in humans.

• MeSH
• embryonální vývoj účinky léků   MeSH
• fenoly toxicita   MeSH
• metylace DNA účinky léků   MeSH
• myši inbrední ICR MeSH
• oocyty účinky léků   metabolismus   MeSH
• poškození DNA MeSH
• stanovení celkové genové exprese MeSH
• sulfony toxicita   MeSH
• těhotenství MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Synthetic progestins are emerging contaminants of the aquatic environment with endocrine disrupting potential. The main aim of the present study was to investigate the effects of the synthetic progestins gestodene, and drospirenone on sex differentiation in common carp (Cyprinus carpio) by histological analysis. To gain insights into the mechanisms behind the observations from the in vivo experiment on sex differentiation, we analyzed expression of genes involved in hypothalamus-pituitary-gonad (HPG) and hypothalamus-pituitary-thyroid (HPT) axes, histology of hepatopancreas, and in vitro bioassays. Carp were continuously exposed to concentrations of 2 ng/L of single progestins (gestodene or drospirenone) or to their mixture at concentration 2 ng/L of each. The exposure started 24 h after fertilization of eggs and concluded 160 days post-hatching. Our results showed that exposure of common carp to a binary mixture of drospirenone and gestodene caused increased incidence of intersex (32%) when compared to clean water and solvent control groups (both 3%). Intersex most probably was induced by a combination of multiple modes of action of the studied substances, namely anti-gonadotropic activity, interference with androgen receptor, and potentially also with HPT axis or estrogen receptor.

• MeSH
• androsteny toxicita   MeSH
• chemické látky znečišťující vodu toxicita   MeSH
• endokrinní disruptory toxicita   MeSH
• gonády účinky léků   MeSH
• hepatopankreas účinky léků   MeSH
• hypofýza účinky léků   MeSH
• hypothalamus účinky léků   MeSH
• kapři růst a vývoj   MeSH
• norpregneny toxicita   MeSH
• sexuální diferenciace účinky léků   genetika   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Synthetic compounds that mimic the action of juvenile hormones (JHs) are founding members of a class of insecticides called insect growth regulators (IGRs). Like JHs, these juvenoids block metamorphosis of insect larvae to reproductive adults. Many biologically active juvenoids deviate in their chemical structure considerably from the sesquiterpenoid JHs, raising questions about the mode of action of such JH mimics. Despite the early deployment of juvenoid IGRs in the mid-1970s, their molecular effect could not be understood until recent discoveries of JH signaling through an intracellular JH receptor, namely the ligand-binding transcription factor Methoprene-tolerant (Met). Here, we briefly overview evidence defining three widely employed and chemically distinct juvenoid IGRs (methoprene, pyriproxyfen, and fenoxycarb), as agonist ligands of the JH receptor. We stress that knowledge of the target molecule is critical for using these compounds both as insecticides and as research tools.

• MeSH
• biologická proměna účinky léků   MeSH
• fenylkarbamáty metabolismus   farmakologie   MeSH
• insekticidy chemie   metabolismus   farmakologie   MeSH
• juvenilní hormony agonisté   chemie   farmakologie   MeSH
• ligandy MeSH
• methopren metabolismus   farmakologie   MeSH
• pyridiny metabolismus   farmakologie   MeSH
• rezistence k insekticidům MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Di-(2-ethylhexyl)-phthalate (DEHP) is a compound widely used as a plasticizer, which can leach from plastics into the environment and thus influence human health. The aim of this study was to analyze whether exposure to an environmentally relevant dose of DEHP during mice fetal development or puberty can cause long-lasting changes detectable month/s after the last exposure. We used a DEHP concentration relevant to a daily human intake of 2.4-3 μg/kg of body weight/day. CD1 outbred mice were treated either in utero or postnatally during puberty and analyzed in adulthood. Analyzing fertility parameters using morphometric, histologic, genomic and proteomic methods we showed that DEHP exposure leads to decreased sperm concentration and quality, in both experimental groups. Moreover, the changes in anogenital distance, seminal vesicle weight, and testicular gene expression suggest a disturbance of androgen signaling in exposed animals. In conclusion, we hereby present, that the prenatal and pubertal exposure to a low dose of DEHP negatively influenced reproductive endpoints in male mice, and some of the effects were persistent until adulthood.

• MeSH
• anální kanál anatomie a histologie   účinky léků   MeSH
• diethylhexylftalát toxicita   MeSH
• endokrinní disruptory toxicita   MeSH
• maternofetální výměna látek MeSH
• mužské pohlavní orgány anatomie a histologie   účinky léků   MeSH
• myši inbrední ICR MeSH
• pohlavní dospělost účinky léků   MeSH
• spermie účinky léků   MeSH
• těhotenství MeSH
• testis anatomie a histologie   účinky léků   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• změkčovadla toxicita   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   genetika   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Parasitic nematodes transition between dramatically different free-living and parasitic stages, with correctly timed development and migration crucial to successful completion of their lifecycle. However little is known of the mechanisms controlling these transitions. microRNAs (miRNAs) negatively regulate gene expression post-transcriptionally and regulate development of diverse organisms. Here we used microarrays to determine the expression profile of miRNAs through development and in gut tissue of the pathogenic nematode Haemonchus contortus. Two miRNAs, mir-228 and mir-235, were enriched in infective L3 larvae, an arrested stage analogous to Caenorhabditis elegans dauer larvae. We hypothesized that these miRNAs may suppress development and maintain arrest. Consistent with this, inhibitors of these miRNAs promoted H. contortus development from L3 to L4 stage, while genetic deletion of C. elegans homologous miRNAs reduced dauer arrest. Epistasis studies with C. elegans daf-2 mutants showed that mir-228 and mir-235 synergise with FOXO transcription factor DAF-16 in the insulin signaling pathway. Target prediction suggests that these miRNAs suppress metabolic and transcription factor activity required for development. Our results provide novel insight into the expression and functions of specific miRNAs in regulating nematode development and identify miRNAs and their target genes as potential therapeutic targets to limit parasite survival within the host.

• MeSH
• Caenorhabditis elegans genetika   MeSH
• cholesteny farmakologie   MeSH
• delece genu MeSH
• druhová specificita MeSH
• genová ontologie MeSH
• Haemonchus účinky léků   genetika   růst a vývoj   MeSH
• larva MeSH
• messenger RNA genetika   metabolismus   MeSH
• mikro RNA biosyntéza   genetika   MeSH
• proteiny Caenorhabditis elegans genetika   MeSH
• receptor inzulinu genetika   MeSH
• RNA helmintů biosyntéza   genetika   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hydrogen peroxide promotes seed germination, but the molecular mechanisms underlying this process are unclear. This study presents the results of eggplant (Solanum melongena) germination analyses conducted at two different temperatures and follows the effect of hydrogen peroxide treatment on seed germination and the seed proteome. Hydrogen peroxide was found to promote eggplant germination in a way not dissimilar to that of increased temperature stimuli. LC-MS profiling detected 729 protein families, 77 of which responded to a temperature increase or hydrogen peroxide treatment. These differentially abundant proteins were found to be involved in a number of processes, including protein and amino acid metabolism, carbohydrate metabolism, and the glyoxylate cycle. There was a very low overlap between hydrogen peroxide and temperature-responsive proteins, highlighting the differences behind the seemingly similar outcomes. Furthermore, the observed changes from the seed proteome indicate that hydrogen peroxide treatment diminished the seed endogenous hydrogen peroxide pool and that a part of manifested positive hydrogen peroxide effect might be related to altered sensitivity to abscisic acid.

• MeSH
• chromatografie kapalinová MeSH
• fyziologický stres účinky léků   MeSH
• hmotnostní spektrometrie MeSH
• klíčení účinky léků   MeSH
• metabolismus sacharidů účinky léků   MeSH
• peroxid vodíku farmakologie   MeSH
• regulace genové exprese u rostlin účinky léků   MeSH
• rostlinné proteiny metabolismus   MeSH
• Solanum melongena účinky léků   fyziologie   MeSH
• teplota MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH

Caspases have functions particularly in apoptosis and inflammation. Increasing evidence indicates novel roles of these proteases in cell differentiation, including those involved in osteogenesis. This investigation provides a complex screening of osteogenic markers affected by pan caspase inhibition in micromass cultures derived from mouse forelimbs. PCR Array analysis showed significant alterations in expression of 49 osteogenic genes after 7 days of inhibition. The largest change was a decrease in CD36 expression, which was confirmed at organ level by caspase inhibition in cultured mouse ulnae followed by CD36 immunohistochemical analysis. So far, available data point to osteogenic potential of pro-apoptotic caspases. Therefore, the expression of pro-apoptotic caspases (-3, -6, -7, -8, -9) within the growth plate of mouse forelimbs at the stage where the individual zones are clearly apparent was studied. Caspase-9 was reported in the growth plate for the first time as well as caspase-6 and -7 in the resting zone, caspase-7 in the proliferation, and caspase-6 and -8 in the ossification zone. For all caspases, there was a gradient increase in activation toward the ossification zone. The distribution of staining varied significantly from that of apoptotic cells, and thus, the results further support non-apoptotic participation of caspases in osteogenesis.

• MeSH
• antigeny CD36 analýza   genetika   MeSH
• imunohistochemie MeSH
• inhibitory kaspas farmakologie   MeSH
• kaspasy metabolismus   MeSH
• kultivované buňky MeSH
• myši MeSH
• orgánové kultury - kultivační techniky MeSH
• osteogeneze * účinky léků   MeSH
• přední končetina růst a vývoj   metabolismus   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Equilibrative ( SLC29A) and concentrative ( SLC28A) nucleoside transporters contribute to proper placental development and mediate uptake of nucleosides/nucleoside-derived drugs. We analyzed placental expression of SLC28A mRNA during gestation. Moreover, we studied in choriocarcinoma-derived BeWo cells whether SLC29A and SLC28A mRNA levels can be modulated by activity of adenylyl cyclase, retinoic acid receptor activation, CpG islands methylation, or histone acetylation, using forskolin, all- trans-retinoic acid, 5-azacytidine, and sodium butyrate/sodium valproate, respectively. We found that expression of SLC28A1, SLC28A2, and SLC28A3 increases during gestation and reveals considerable interindividual variability. SLC28A2 was shown to be a dominant subtype in the first-trimester and term human placenta, while SLC28A1 exhibited negligible expression in the term placenta only. In BeWo cells, we detected mRNA of SLC28A2 and SLC28A3. Levels of the latter were affected by 5-azacytidine and all- trans-retinoic acid, while the former was modulated by sodium valproate (but not sodium butyrate), all- trans-retinoic acid, 5-azacytidine, and forskolin that caused 25-fold increase in SLC28A2 mRNA; we documented by analysis of syncytin-1 that the observed changes in SLC28A expression do not correlate with the morphological differentiation state of BeWo cells. Upregulated SLC28A2 mRNA was reflected in elevated uptake of [3H]-adenosine, high-affinity substrate of concentrative nucleoside transporter 2. Using KT-5720 and inhibitors of phosphodiesterases, we subsequently confirmed importance of cAMP/protein kinase A pathway in SLC28A2 regulation. On the other hand, SLC29A genes exhibited constitutive expression and none of the tested compounds increased SLC28A1 expression to detectable levels. In conclusion, we provide the first evidence that methylation status and activation of retinoic acid receptor affect placental SLC28A2 and SLC28A3 transcription and substrates of concentrative nucleoside transporter 2 might be taken up in higher extent in placentas with overactivated cAMP/protein kinase A pathway and likely in the term placenta.

• MeSH
• buněčná diferenciace účinky léků   fyziologie   MeSH
• ekvilibrační proteiny přenášející nukleosidy genetika   metabolismus   MeSH
• gestační stáří * MeSH
• karbazoly farmakologie   MeSH
• lidé MeSH
• membránové transportní proteiny genetika   metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• nádorové buněčné linie MeSH
• placenta účinky léků   metabolismus   MeSH
• pyrroly farmakologie   MeSH
• těhotenství MeSH
• upregulace MeSH
• vývojová regulace genové exprese účinky léků   fyziologie   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Juvenile hormones (JH) and ecdysteroids regulate many biological and metabolic processes. CREB-binding protein (CBP) is a transcriptional co-regulator with histone acetyltransferase (HAT) activity. Therefore, CBP is involved in activation of many transcription factors that regulate expression of genes associated with postembryonic development in insects. However, the function of CBP in JH action in insects is not well understood. Hence, we studied the role of CBP in JH action in the red flour beetle, Tribolium castaneum and the Tribolium cell line. CBP knockdown caused a decrease in JH induction of genes, Kr-h1, 4EBP and G13402 in T. castaneum larvae, adults and TcA cells whereas, Trichostatin A [TSA, a histone deacetylase (HDAC) inhibitor] induced the expression of these JH-response genes. Western blot analysis with specific antibodies revealed the requirement of CBP for the acetylation of H3K18 and H3K27 in both T. castaneum and TcA cells. Chromatin immunoprecipitation (Chip) assays showed the importance of CBP-mediated acetylation of H3K27 for JH induction of Kr-h1, 4EBP, and G13402 in TcA cells. These data suggest that CBP plays an important role in JH action in the model insect, T.castaneum.

• MeSH
• acetylace MeSH
• genový knockout MeSH
• histony metabolismus   MeSH
• hmyzí proteiny genetika   metabolismus   MeSH
• juvenilní hormony farmakologie   MeSH
• protein vázající CREB genetika   metabolismus   MeSH
• Tribolium genetika   růst a vývoj   metabolismus   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

The formation of the vertebrate brain requires the generation, migration, differentiation and survival of neurons. Genetic mutations that perturb these critical cellular events can result in malformations of the telencephalon, providing a molecular window into brain development. Here we report the identification of an N-ethyl-N-nitrosourea-induced mouse mutant characterized by a fractured hippocampal pyramidal cell layer, attributable to defects in neuronal migration. We show that this is caused by a hypomorphic mutation in Vps15 that perturbs endosomal-lysosomal trafficking and autophagy, resulting in an upregulation of Nischarin, which inhibits Pak1 signaling. The complete ablation of Vps15 results in the accumulation of autophagic substrates, the induction of apoptosis and severe cortical atrophy. Finally, we report that mutations in VPS15 are associated with cortical atrophy and epilepsy in humans. These data highlight the importance of the Vps15-Vps34 complex and the Nischarin-Pak1 signaling hub in the development of the telencephalon.

• MeSH
• alkylační látky toxicita   MeSH
• atrofie chemicky indukované   genetika   patologie   MeSH
• autofagie účinky léků   genetika   MeSH
• embryo savčí MeSH
• ethylnitrosomočovina toxicita   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• mozek účinky léků   patologie   MeSH
• mutace účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• neurony účinky léků   patologie   ultrastruktura   MeSH
• neurovývojové poruchy * chemicky indukované   diagnostické zobrazování   genetika   patologie   MeSH
• novorozená zvířata MeSH
• pohyb buněk účinky léků   genetika   MeSH
• signální transdukce účinky léků   genetika   MeSH
• vakuolární protonové ATPasy účinky léků   genetika   MeSH
• vývojová regulace genové exprese účinky léků   genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH