The problem of the functioning specificity of sex chromosomes during the early stages of embryogenesis in man and the associated problem of the sex ratio in spontaneous and induced abortions, as well as in newborns, remains open. We have conducted a cytogenetic examination of 342 spontaneous abortions divided into three clinical groups on the basis of the severity of the developmental disturbances of the embryo: spontaneous abortions sensu stricto with a developed embryo without any significant intrauterine delay of development (n = 100), nondeveloping pregnancies (n = 176), and anembryonic fetuses (n = 66). The frequency of chromosomal mutations in these groups was 22.0, 48.3, and 48.5%, respectively. Statistical analysis has demonstrated significant differences between the studied groups in the frequencies of the normal and abnormal karyotypes: the major contributions to these differences were associated with autosomal trisomy, triploidy, and 46,XY karyotype. The presence of 46,XY may reflect specific genetic mechanisms of prenatal mortality of embryos with normal karyotype, associated with sex and/or with the imprinting of X-chromosomes. The sex ratio in spontaneous abortions with normal karyotype was as follows: 0.77 for spontaneous abortions with well-developed embryos without any significant intrauterine delay of development; 0.60 for non-developing pregnancies; and 0.31 for anembryonic fetuses. An analysis of DNA from the embryos and their parents has demonstrated a low probability of contamination of cell cultures with mother cells as a possible source of prevalence of embryos with 46,XX karyotype among spontaneous abortions. Nondeveloping pregnancies and anembryonic fetuses showed statistically significant differences in the sex ratio (1.11) from the control group consisting of medical abortions. Differences in the sex ratio were due to an increasingly lower proportion of embryos with karyotype 46,XY (relative to the expected one) among the fetuses with an increased severity of developmental disturbances. The statistical "chances ratio" index also provided evidence that embryos with 46,XY karyotype had a higher propensity to produce a well-formed fetus as compared with the female embryos. We propose that the expression of genes of the maternal X-chromosome in XY embryos supports a more stable development during early embryogenesis as compared with XX embryos. In the latter case, normal development is coupled with the operation of an additional mechanism for compensation of the dose of X-linked genes. Operation of this mechanism increases the probability of disturbances in female embryos. A higher viability of XY embryos during the early stages of ontogenesis in man appears to explain their underrepresentation in samples of spontaneously aborted embryos and appears to be the major factor responsible for the deviation of the sex ratio from the theoretically expected value.

Abortion, Spontaneous↗

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[Evaluation of the role of uniparental disomy in early embryolethality of man].

We carried out systematic studies of the contribution of uniparental disomy for eight human chromosomes, 2, 9, 11, 15, 16, 19, 20, and 21, to the etiology of spontaneous mortality of human embryos. Most of these chromosomes have regions with orthologous imprinted genes syntenic with those on mouse chromosomes, the disturbed expression of which is related to embryolethality in mice. Screening of uniparental disomy in spontaneous 5- to 16-week abortuses was performed by evaluation of the pattern of inheritance of alleles of polymorphic microsatellite loci located in the studied chromosomes. A total of 100 human embryos with cytogenetically determined normal karyotype were studied, in which arrest at the early stages of intrauterine development was determined by ultrasound examination of pregnant women. During this study, 13 embryos were discarded due to karyotype anomalies or nonpaternity. No cases of uniparental disomy were found among the 87 studied abortuses for any of chromosomes studied. The analysis of the results of this study and four other studies concerning the search for uniparental disomy in dead embryos and fetuses did not reveal its elevated frequency in spontaneous abortuses as compared to the theoretically expected value based on evaluation of the probable combination of meiotic errors in human gametes. The data we obtained suggest that, first, uniparental disomies for human chromosomes that have regions with orthologous imprinted genes syntenic with mouse chromosomes do not contribute noticeably to the death of human embryos at the early developmental stages and, second, the mechanisms underlying embryolethality as a result of disturbed expression of imprinted loci differ markedly in mammals evolutionarily remote from one other.

Abortion, Spontaneous↗

PubMedDate not supplied

[RNA polymerase III transcription apparatus: structure and transcription regulation].

RNA polymerase III is a complex multi-subunit enzyme directing transcription of small stable non-translated RNA genes: tRNAs, 5S rRNA, Alu-RNA, U6 snRNA genes and some others (class III genes). Because of its complexity the enzyme is the worst studied among three forms of eukariotic RNA polymerases, but it draws more attention of the researchers in recent years. The reason is that new data appeared about an essential role of RNA polymerase III RNA products in such important cell processes as growth, proliferation and differentiation. It was shown that the RNA product levels are changed depending on cell growth rate and cell cycle stage, during cancer transformation, virus infection and heat shock, and either depend on physiological state of the cell (slow and active proliferation and apoptosis). In this review we consider the structure and function of RNA polymerase III, its general transcription factors and holoenzyme, the structure of different class III gene promoters, the preinitiation complex assembly and the transcription cycle. The second part of the review is devoted to the regulation of class III gene transcription in dependence on cell cycle stage, growth factor influence and cell growth rate, during cell transformation and apoptosis.

Cell Cycle↗

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[Computational search for potential post-translational modification sites in human RNA polymerase III subunits].

The transcription of small stable non-translated RNA genes (class III genes), directed by RNA polymerase III, is strictly regulated in accordance to physiological state of the cell (growth rate, cell cycle stage, apoptosis, etc.) Post-translational modifications of the polymerase may play the important role in class III gene transcription regulation. Using computational programs searching for potential post-translational modifications sites in proteins (MotifScan, NetPhos 2.0, and Yin-Yan 1.2), possible sites of phosphorylation were identified in all 17 subunits of human RNA polymerase III, and possible sites of reciprocal phosphorylation and glycosilation ("yin-yan" sites) - in 13 subunits. Among the identified sites -17 sites of phosphorylation in seven subunits are conservative in human, Saccharomyces cerevisiae and Schizosaccharomyces pombe, including two "yin-yan" sites in two subunits. The data obtained can be used for experimental identification of RNA polymerase III modification sites in vivo in cells being in different physiological states.

Computational Biology↗

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