1,720,979 research outputs found
X-Chromosome Inactivation during Preimplantation Development and in Pluripotent Stem Cells
No full textX dosage compensation between XX female and XY male mammalian cells is achieved by a process known as X-chromosome inactivation (XCI). XCI initiates early during preimplantation development in female cells, and it is subsequently stably maintained in somatic cells. However, XCI is a reversible process that occurs in vivo in the inner cell mass of the blastocyst, in primordial germ cells or in spermatids during reprogramming. Erasure of transcriptional gene silencing can occur though a mechanism named X-chromosome reactivation (XCR). XCI and XCR have been substantially deciphered in the mouse, whereas they still remain debated in the human. In this review, we summarized the recent advances in the knowledge of X-linked gene dosage compensation during mouse and human preimplantation development and in pluripotent stem cells
Building Pluripotency Identity in the Early Embryo and Derived Stem Cells
No full textThe fusion of two highly differentiated cells, an oocyte with a spermatozoon, gives rise
to the zygote, a single totipotent cell, which has the capability to develop into a complete, fully
functional organism. Then, as development proceeds, a series of programmed cell divisions occur
whereby the arising cells progressively acquire their own cellular and molecular identity, and
totipotency narrows until when pluripotency is achieved. The path towards pluripotency involves
transcriptome modulation, remodeling of the chromatin epigenetic landscape to which external
modulators contribute. Both human and mouse embryos are a source of different types of pluripotent
stem cells whose characteristics can be captured and maintained in vitro. The main aim of this review
is to address the cellular properties and the molecular signature of the emerging cells during mouse
and human early development, highlighting similarities and differences between the two species
and between the embryos and their cognate stem cells
Functional and structural phenotyping of cardiomyocytes in the 3D organization of embryoid bodies exposed to arsenic trioxide
No full textChronic exposure to environmental pollutants threatens human health. Arsenic, a world-wide diffused toxicant, is associated to cardiac pathology in the adult and to congenital heart defects in the foetus. Poorly known are its effects on perinatal cardiomyocytes. Here, bioinformatic image-analysis tools were coupled with cellular and molecular analyses to obtain functional and structural quantitative metrics of the impairment induced by 0.1, 0.5 or 1.0 μM arsenic trioxide exposure on the perinatal-like cardiomyocyte component of mouse embryoid bodies, within their 3D complex cell organization. With this approach, we quantified alterations to the (a) beating activity; (b) sarcomere organization (texture, edge, repetitiveness, height and width of the Z bands); (c) cardiomyocyte size and shape; (d) volume occupied by cardiomyocytes within the EBs. Sarcomere organization and cell morphology impairment are paralleled by differential expression of sarcomeric α-actin and Tropomyosin proteins and of acta2, myh6 and myh7 genes. Also, significant increase of Cx40, Cx43 and Cx45 connexin genes and of Cx43 protein expression profiles is paralleled by large Cx43 immunofluorescence signals. These results provide new insights into the role of arsenic in impairing cytoskeletal components of perinatal-like cardiomyocytes which, in turn, affect cell size, shape and beating capacity
A putative 2n=26 Robertsonian mouse embryonic stem cell line maintains its karyotype stability when cultured up to passage 28
No full textChronic cypermethrin exposure alters mouse embryonic stem cell growth kinetics, induces Phase II detoxification response and affects pluripotency and differentiation gene expression
Full text linkWorldwide uncontrolled use of synthetic pyrethroids contaminates water and soil leading to health hazards. Cypermethrin (CYP), the most used pyrethroid, induces detrimental effects on adults and embryos at different stages of development of several vertebrate species. In Mammals, CYP-induced alterations have been previously described in adult somatic cells and in post-implantation embryos. It remains unknown whether CYP has effects during pre-implantation development. Studies to access pre-implantation embryo toxicity are complicated by the restricted number of blastocysts that may be obtained, either in vivo or in vitro. Embryonic stem cells (ESCs) are an in vitro model study that overcomes these limitations, as millions of pluripotent cells are available to the analysis. Also, ESCs maintain the same pluripotency characteristics and differentiation capacity of the inner cell mass (ICM) present in the blastocyst, from which they derive. In this work, using mouse R1 ESCs, we studied CYP-induced cell death, ROS production, the activation of oxidative stress-related and detoxification responses and the population growth kinetics following 72 h exposure at the 0.3 mM LD50 dose. Also, the expression levels of pluripotency genes in exposed ESCs and of markers of the three germ layers after their differentiation into embryoid bodies (EBs) were determined. Two apoptotic waves were observed at 12-24 h and at 72 h. The increase of ROS production, at 24 h until the end of the culture period, was accompanied by the induction, at 48 h, of redox-related Cat, Sod1, Sod2, Gpx1 and Gpx4 genes. Up-regulation of Cyp1b1, but not of Cyp1a1, phase I gene was detected at 72 h and induction of Nqo1, Gsta1 and Ugt1a6 phase II genes began at 24 h exposure. The results show that exposed R1 ESCs activate oxidative stress-related and detoxification responses, although not sufficient, during the culture period tested, to warrant recovery of the growth rate observed in untreated cells. Also, CYP exposure altered the expression of Oct-4 and Nanog pluripotency genes in ESCs and, when differentiated into EBs, the expression of Fgf5, Brachyury and Foxa2, early markers of the ectoderm, mesoderm and endoderm germ layers, respectively. NIH/3T3 cells, a differentiated cell line of embryonic origin, were used for comparison
Multi- and Transgenerational Effects of Environmental Toxicants on Mammalian Reproduction
No full textEnvironmental toxicants (ETs) are an exogenous chemical group diffused in the environment
that contaminate food, water, air and soil, and through the food chain, they bioaccumulate
into the organisms. In mammals, the exposure to ETs can affect both male and female fertility and
their reproductive health through complex alterations that impact both gametogeneses, among other
processes. In humans, direct exposure to ETs concurs to the declining of fertility, and its transmission
across generations has been recently proposed. However, multi- and transgenerational inheritances of
ET reprotoxicity have only been demonstrated in animals. Here, we review recent studies performed
on laboratory model animals investigating the effects of ETs, such as BPA, phthalates, pesticides and
persistent contaminants, on the reproductive system transmitted through generations. This includes
multigenerational effects, where exposure to the compounds cannot be excluded, and transgenerational
effects in unexposed animals. Additionally, we report on epigenetic mechanisms, such as DNA
methylation, histone tails and noncoding RNAs, which may play a mechanistic role in a nongenetic
transmission of environmental information exposure through the germline across generations
Karyotype analysis of the euploid cell population of a mouse embryonic stem cell line revealed a high incidence of chromosome abnormalities that varied during culture
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