Comparative dynamics of 5-methylcytosine reprogramming and TET family expression during preimplantation mammalian development in mouse and sheep.

Despite previous assumption that paternal active DNA demethylation is an evolutionary conserved phenomenon in mammals, emerging studies in other species, particularly sheep, do not support this issue. Recently, ten eleven translocation (TET) enzymes have been suggested as intermediates in genome-wide DNA demethylation through the iterative conversion of five methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC)/5-formylcytosine/5-carboxylcytosine (5caC) derivatives. This study investigated whether TET enzymes and 5mC derivatives are also involved in dynamic reprogramming of early sheep embryos derived by fertilization. Mouse zygotes and developing embryos were considered as control. Obtained results reported substantial differences in dynamics of parent-of-origin-specific patterns of 5mC reprogramming and generation/dilution of 5mC derivatives (5hmC and 5caC) between mouse and sheep early zygotes. Sheep zygotes reported a gradual and insignificant decrease pattern of parental pronucleus 5mC, which was notably replication independent, coincided with gradual generation of 5hmC and 5caC. Although the expression profiles of TET family of enzymes (Tet1, Tet2, and Tet3), with the main exception being Tet2 at later developmental stages, were similar between mouse and sheep developing embryos. In addition, although the expression level of Tet3 was higher than Tet1 and Tet2 in MII oocytes and zygotes in both mouse and sheep, the expression of Tet3 in mouse was higher than sheep in both MII oocytes and zygotes. The contrasting dynamics of 5mC reprogramming between these two species may be associated with the particular evolutionary differences that exist between developmental program of rodents and ruminants, particularly during peri-implantation stages.

Enantiodromic effective generators of a Markov jump process with Gallavotti-Cohen symmetry.

This paper deals with the properties of the stochastic generators of the effective (driven) processes associated with atypical values of transition-dependent time-integrated currents with Gallavotti-Cohen symmetry in Markov jump processes. Exploiting the concept of biased ensemble of trajectories by introducing a biasing field s, we show that the stochastic generators of the effective processes associated with the biasing fields s and E-s are enantiodromic with respect to each other where E is the conjugated field to the current. We illustrate our findings by considering an exactly solvable creation-annihilation process of classical particles with nearest-neighbor interactions defined on a one-dimensional lattice.

A physiological, rather than a superovulated, post-implantation environment can attenuate the compromising effect of assisted reproductive techniques on gene expression in developing mice embryos.

Assisted reproductive techniques (ARTs) may perturb the pre-/peri-conception microenvironments, which subsequently threaten the health of offspring. This study aimed to investigate the effects of superovulation, vitrification, in vitro culture, and embryo transfer on the expression of epigenetic modulators, imprinted genes, and pluripotency markers in expanded blastocysts and Day-9.5 (D9.5) concepti. Results revealed that 53.4% (8/15) and 86.7% (13/15) of genes in the fetus and placenta, respectively, have similar patterns of transcription in all D9.5 concepti, despite the perturbed mRNA expression observed at the blastocyst stage for each embryo-production technique. These observations indicate a counterbalancing of the abnormal expression pattern analyzed at the blastocyst stage during post-implantation development, particularly when the uterus of a naturally synchronized foster mother is employed. Superovulation resulted in the most abnormal expression patterns compared to other treatment groups, although these same blastocysts were able to develop in a synchronized uterus. Thus, superovulation creates a hormonal environment that negatively affected gene expression and impairs fetal growth more adversely during post-implantation development than other ART protocols, such as in vitro culture, vitrification, or embryo transfer-although each did contribute negatively to the implantation and development process. Together, these results may have implications for treating infertility in humans.

Effect of epigenetic modification with trichostatin A and S-adenosylhomocysteine on developmental competence and POU5F1-EGFP expression of interspecies cloned embryos in dog.

Adult canine fibroblasts stably transfected with either cytomegalovirus (CMV) or POU5F1 promoter-driven enhanced green fluorescent protein (EGFP) were used to investigate if pre-treatment of these donor cells with two epigenetic drugs [trichostatin A (TSA), or S-adenosylhomocysteine (SAH)] can improve the efficiency of interspecies somatic cell nuclear transfer (iSCNT). Fluorescence-activated cell sorting (FACS), analyses revealed that TSA, but not SAH, treatment of both transgenic and non-transgenic fibroblasts significantly increased acetylation levels compared with untreated relatives. The expression levels of Bcl2 and P53 were significantly affected in TSA-treated cells compared with untreated cells, whereas SAH treatment had no significant effect on cell apoptosis. Irrespective of epigenetic modification, dog/bovine iSCNT embryos had overall similar rates of cleavage and development to 8-16-cell and morula stages in non-transgenic groups. For transgenic reconstructed embryos, however, TSA and SAH could significantly improve development to 8-16-cell and morula stages compared with control. Even though, irrespective of cell transgenesis and epigenetic modification, none of the iSCNT embryos developed to the blastocyst stage. The iSCNT embryos carrying CMV-EGFP expressed EGFP at all developmental stages (2-cell, 4-cell, 8-16-cell, and morula) without mosaicism, while no POU5F1-EGFP signal was observed in any stage of developing iSCNT embryos irrespective of TSA/SAH epigenetic modifications. These results indicated that bovine oocytes partially remodel canine fibroblasts and that TSA and SAH have marginal beneficial effects on this process.

Particle-current fluctuations in a variant of the asymmetric Glauber model.

We study the total particle-current fluctuations in a one-dimensional stochastic system of classical particles consisting of branching and death processes which is a variant of asymmetric zero-temperature Glauber dynamics. The full spectrum of a modified Hamiltonian, whose minimum eigenvalue generates the large deviation function for the total particle-current fluctuations through a Legendre-Fenchel transformation, is obtained analytically. Three examples are presented and numerically exact results are compared to our analytical calculations.

Temporal evolution of product shock measures in the totally asymmetric simple exclusion process with sublattice-parallel update.

It is known that when the steady state of a one-dimensional multispecies system, which evolves via a random-sequential updating mechanism, is written in terms of a linear combination of Bernoulli shock measures with random-walk dynamics, it can be equivalently expressed as a matrix-product state. In this case the quadratic algebra of the system always has a two-dimensional matrix representation. Our investigations show that this equivalence exists at least for the systems with deterministic sublattice-parallel update. In this paper we consider the totally asymmetric simple exclusion process on a finite lattice with open boundaries and sublattice-parallel update as an example.

Repelling random walkers in a diffusion-coalescence system.

We have shown that the steady state probability distribution function of a diffusion-coalescence system on a one-dimensional lattice of length L with reflecting boundaries can be written in terms of a superposition of double-shock structures which perform biased random walks on the lattice while repelling each other. The shocks can enter into the system and leave it from the boundaries. Depending on the microscopic reaction rates, the system is known to have two different phases. We have found that the mean distance between the shock positions is of order L in one phase while it is of order 1 in the other phase.

Effect of GnRH on guinea pig endometrium at preimplantation stage.

Endometrium of GnRH treated group resembled with pregnant group and endometrial thickness in these groups significantly increased in comparison with non-pregnant group. In GnRH treated animals, most of histomorphological changes in epithelial cells, glands and stroma of uterus was similar to pregnant group. The results revealed that mammalian form of GnRH exerted endometrial change in guinea pig almost similar to those occur in normal pregnant animals and its administration prior to implantation may improve pregnancy rate following embryo transfer.

Exact solution of a reaction-diffusion model with particle-number conservation.

We analytically investigate a one-dimensional branching-coalescing model with reflecting boundaries in a canonical ensemble where the total number of particles on the chain is conserved. Exact analytical calculations show that the model has two different phases which are separated by a second-order phase transition. The thermodynamic behavior of the canonical partition function of the model has been calculated exactly in each phase. Density profiles of particles have also been obtained explicitly. It is shown that the exponential part of the density profiles decays on three different length scales which depend on the total density of particles.