Gametes of both sexes (sperm and oocyte) are highly specialized and differentiated but within a very short time period post-fertilization the embryonic genome, produced by the combination of the two highly specialized parental genomes, is completely converted into a totipotent state. As a result, the one-cell-stage embryo can give rise to all cell types of all three embryonic layers, including the gametes. Thus, it is evident that extensive and efficient reprogramming steps occur soon after fertilization and also probably during early embryogenesis to reverse completely the differentiated state of the gamete and to achieve toti- or later on pluripotency of embryonic cells. However, after the embryo reaches the blastocyst stage, the first two distinct cell lineages can be clearly distinguished--the trophectoderm and the inner cells mass. The de-differentiation of gametes after fertilization, as well as the differentiation that is associated with the formation of blastocysts, are accompanied by changes in the state and properties of chromatin in individual embryonic nuclei at both the whole genome level as well as at the level of individual genes. In this contribution, we focus mainly on those events that take place soon after fertilization and during early embryogenesis in mammals. We will discuss the changes in DNA methylation and covalent histone modifications that were shown to be highly dynamic during this period; moreover, it has also been documented that abnormalities in these processes have a devastating impact on the developmental ability of embryos. Special attention will be paid to somatic cell nuclear transfer as it has been shown that the aberrant and inefficient reprogramming may be responsible for compromised development of cloned embryos.
- MeSH
- blastocysta metabolismus MeSH
- buněčná diferenciace MeSH
- buněčné jádro genetika MeSH
- chromatin genetika metabolismus patologie MeSH
- dediferenciace buněk MeSH
- embryonální vývoj genetika MeSH
- genetické nemoci vrozené etiologie MeSH
- histony genetika MeSH
- klonování organismů škodlivé účinky MeSH
- lidé MeSH
- metylace DNA MeSH
- morula metabolismus MeSH
- pluripotentní kmenové buňky MeSH
- přeprogramování buněk genetika MeSH
- savci MeSH
- stadium rýhování vajíčka metabolismus MeSH
- techniky jaderného přenosu škodlivé účinky normy MeSH
- totipotentní kmenové buňky MeSH
- vývojová regulace genové exprese MeSH
- zárodečné buňky metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- chromatin MeSH
- histony MeSH
OBJECTIVE: To evaluate the number of micronuclei in snake-like chromatin (SLC) cells in the conjunctival epithelium of keratoconjunctivitis sicca (KCS) patients. To elucidate possible correlations between SLC cell numbers and KCS intensity. STUDY DESIGN: Impression cytology specimens from the bulbar conjunctiva of healthy controls and KCS patients were harvested and divided into 3 groups: group 1, controls; group 2, KCS SLC-negative; and group 3, KCS SLC-positive. The number of micronuclei (MNi) in SLC-negative and SLC-positive epithelial cells of each group was counted. RESULTS: The number of MNi in SLC-negative cells of groups 1 and 2 did not exceed 1 MNi/1,000 cells. A significant increase in the frequency of micronuclei in the upper bulbar conjunctiva was noted in SLC-positive (14.75 +/- 8.09 MNi/1,000 cells) as well as SLC-negative cells (4.0 +/- 3.83 MNi/1,000 cells) of group 3. CONCLUSION: We demonstrate here that the presence of MNi in the conjunctival epithelium of KCS patients could be a characteristic feature accompanying SLC cells. The fact that increased numbers of SLC cells correlates with impaired values in clinical test as well as decreased goblet and epithelial cell densities confirms that the presence of SLC cells correlates with KCS intensity.
- MeSH
- chromatin patologie MeSH
- epitelové buňky patologie MeSH
- konjunktiva patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metaplazie MeSH
- mikrojaderné testy MeSH
- mikrojádra chromozomálně defektní * MeSH
- počet buněk MeSH
- pohárkové buňky patologie MeSH
- slzy fyziologie MeSH
- studie případů a kontrol MeSH
- suchá keratokonjunktivitida patologie patofyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chromatin MeSH
BACKGROUND: This study examined potential associations between exposure to episodes of air pollution and alterations in semen quality. The air pollution, resulting from combustion of coal for industry and home heating in the Teplice district of the Czech Republic, was much higher during the winter than at other times of year with peaks exceeding US air quality standards. METHODS: Young men from Teplice were sampled up to seven times over 2 years allowing evaluation of semen quality after periods of exposure to both low and high air pollution. Routine semen analysis (sperm concentration, motility and morphology) and tests for sperm aneuploidy and chromatin integrity were performed, comparing measurements within each subject. Exposure was classified as high or low based on data from ambient air pollution monitoring. RESULTS: Using repeated measures analysis, a significant association was found between exposure to periods of high air pollution (at or above the upper limit of US air quality standards) and the percentage of sperm with DNA fragmentation according to sperm chromatin structure assay (SCSA). Other semen measures were not associated with air pollution. CONCLUSION: Exposure to intermittent air pollution may result in sperm DNA damage and thereby increase the rates of male-mediated infertility, miscarriage, and other adverse reproductive outcomes.
- MeSH
- aneuploidie MeSH
- biologické markery MeSH
- časové faktory MeSH
- chromatin chemie účinky léků metabolismus patologie MeSH
- DNA účinky léků MeSH
- dospělí MeSH
- fragmentace DNA * MeSH
- kohortové studie MeSH
- kovy MeSH
- látky znečišťující vzduch * MeSH
- lidé MeSH
- mužská infertilita etiologie MeSH
- počet spermií MeSH
- průzkumy a dotazníky MeSH
- samovolný potrat MeSH
- sperma účinky léků metabolismus MeSH
- spermie účinky léků metabolismus patologie MeSH
- statistické modely MeSH
- vystavení vlivu životního prostředí * MeSH
- znečištění ovzduší * MeSH
- znečištění tabákovým kouřem * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- chromatin MeSH
- DNA MeSH
- kovy MeSH
- látky znečišťující vzduch * MeSH
- znečištění tabákovým kouřem * MeSH
Treatment of HL-60 cells with micromolar concentrations of N(6)-benzyladenosine (N(6)-benzylaminopurine riboside [BAPR]) led to the occurrence of apoptosis in a concentration-dependent manner. Incubation period as short as 2 h in the presence of BAPR was sufficient for triggering irreversible changes leading to apoptosis even after the transfer of cells to the standard medium (without BAPR). Cell death induced by BAPR proceeded rapidly and in a very synchronous fashion. Detailed study of temporal changes in a chromatin structure and DNA integrity showed that the movement of chromatin toward the nuclear periphery is the fundamental event within dying cells. We demonstrated that this rearrangement of chromatin is irreversible and it takes place without apparent DNA degradation. The extensive DNA cleavage seems to be a rather late event, as it was observed in cells that exhibited a typical apoptotic morphology (apoptotic bodies). On the basis of temporal changes in the ATP level within dying cells, it is concluded that ATP is essential for the movement of chromatin toward the nuclear envelope but not for the subsequent chromatin condensation leading to the formation of apoptotic bodies. DNA fragmentation also seems to be ATP independent. BAPR interfered with neither pyrimidine nor purine biosynthesis, as none of the tested bases and the corresponding nucleosides prevented or reduced apoptosis in BAPR-treated cells. Adenosine was the only exception that substantially reduced the effect of BAPR. Since transport of exogenous adenosine into cells was essential to manifest its protective effect, we assume that adenosine is a competitive inhibitor of adenosine kinase and thus reduces intracellular phosphorylation of BAPR. Indeed, 4-amino-3-iodo-1(beta-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine, a potent inhibitor of adenosine kinase, fully prevented BAPR-induced apoptosis. These results suggest that cytotoxic effect of BAPR is related to its activation by phosphorylation within cells, rather than to its interaction with extracellular adenosine receptors.
- MeSH
- adenosin analogy a deriváty farmakologie MeSH
- apoptóza účinky léků MeSH
- chromatin účinky léků patologie MeSH
- fosforylace MeSH
- fragmentace DNA účinky léků MeSH
- HL-60 buňky účinky léků metabolismus patologie MeSH
- lidé MeSH
- purinergní receptory P1 metabolismus MeSH
- signální transdukce účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenosin MeSH
- chromatin MeSH
- N(6)-benzyladenosine MeSH Prohlížeč
- purinergní receptory P1 MeSH
The presence of checkpoint mechanisms which are able to recognize damaged chromatin and thereafter to prevent exit from metaphase I has been investigated in giant mouse oocytes produced by fusion of a normal metaphase I oocyte with an equivalent oocyte with damaged chromatin. The presence of damaged chromatin did not prevent the onset of anaphase I in both sets of chromatin in the fused cells. Interestingly, fused or unfused cells containing only damaged chromatin failed to enter anaphase and persisted instead in a metaphase-like state. These results demonstrate the fragility of checkpoint controls in mammalian female germ cells.
- MeSH
- chromatin patologie MeSH
- fúze buněk MeSH
- metafáze * MeSH
- myši MeSH
- oocyty patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- chromatin MeSH
