Similar Datasets
Project description:Arsenite is mainly used as insecticides, antiseptic and herbicides. It enters the food chain through soil contamination, and then impedes human health, including of reproductive systems. Early embryos, as the initial stage of mammalian life, are very sensitive to the environmental toxins and pollutants. However, whether and how arsenite disturbs the early embryo development remains unknown. Here, we used mouse early embryo as a model and found that arsenite exposure did not induce reactive oxygen species production, DNA damage and apoptosis in early mouse embryos. However, arsenite exposure made embryonic development arrest at the 2-cell stage by altering their gene expression patterns. The transcriptional profile in the arrested embryos showed abnormal maternal-to-zygote transition (MZT). More importantly, arsenite exposure attenuated H3K27ac modification enrichment at the promoter region of Brg1 (a key gene for MZT), which inhibited its transcription, and further affected MZT and early embryonic development. Taken together, these results suggest that arsenite exposure affects MZT by reducing the enrichment of H3K27ac on the embryonic genome, and ultimately induces early embryonic development arrest at the 2-cell stage.
2026-01-01 | GSE222535 | GEO
Project description:Arsenite is mainly used as insecticides, antiseptic and herbicides. It enters the food chain through soil contamination, and then impedes human health, including of reproductive systems. Early embryos, as the initial stage of mammalian life, are very sensitive to the environmental toxins and pollutants. However, whether and how arsenite disturbs the early embryo development remains unknown. Here, we used mouse early embryo as a model and found that arsenite exposure did not induce reactive oxygen species production, DNA damage and apoptosis in early mouse embryos. However, arsenite exposure made embryonic development arrest at the 2-cell stage by altering their gene expression patterns. The transcriptional profile in the arrested embryos showed abnormal maternal-to-zygote transition (MZT). More importantly, arsenite exposure attenuated H3K27ac modification enrichment at the promoter region of Brg1 (a key gene for MZT), which inhibited its transcription, and further affected MZT and early embryonic development. Taken together, these results suggest that arsenite exposure affects MZT by reducing the enrichment of H3K27ac on the embryonic genome, and ultimately induces early embryonic development arrest at the 2-cell stage.
2026-01-01 | GSE222534 | GEO
Project description:Arsenite exposure disturbs maternal-to-zygote transition by attenuating H3K27ac during mouse preimplantation development
| PRJNA922478 | ENA
Project description:Arsenite exposure disturbs maternal-to-zygote transition by attenuating H3K27ac during mouse preimplantation development [ChIP-seq]
| PRJNA922481 | ENA
Project description:Arsenite exposure disturbs maternal-to-zygote transition by attenuating H3K27ac during mouse preimplantation development [RNA-seq]
| PRJNA922485 | ENA
Project description:Both epidemiological investigations and animal studies have linked arsenic-contaminated water to cancers, in- cluding skin, liver and lung cancers. Besides genotoxicity, arsenic exposure-related pathogenesis of disease is widely considered through epigenetic mechanisms; however, the underlying mechanism remains to be deter- mined. Herein we explore the initial epigenetic changes via acute sodium arsenite (As) exposures of mouse em- bryonic fibroblast (MEF) cells and histone H3K79 methyltransferase Dot1L knockout (Dot1L− /−) MEF cells. Our RNA-seq and Western blot data demonstrated that, in both cell lines, acute As exposure abolished histone acetyl- transferase p300 at the RNA level and subsequent protein level. Consequently, p300-specific main target histone H3K27ac, a marker separating active from poised enhancers, decreased dramatically as validated by both West- ern blot and ChIP-qPCR/seq analyses. Concomitantly, H3K4me1 as another well-known marker for enhancers also showed significant decreases, suggesting an underappreciated crosstalk between H3K4me1 and H3K27ac involved in As exposure. Significantly, As exposure-reduced H3K27ac and H3K4me1 inhibited the expression of genes including EP300 itself and Kruppel Like Factor 4(Klf4) that both are tumor suppressor genes. Collectively, our investigations identified p300 as an internal bridging factor within cells to sense external environmental As exposure to alter chromatin, thereby changing gene transcription for disease pathogenesis.
2020-12-10 | GSE118827 | GEO
Project description:During the first cell fate decision in mammalian embryos the inner cell mass cells, which will give rise to the embryo proper and other extraembryonic tissues, segregate from the trophectoderm cells, the precursors of the placenta. Cell fate segregation proceeds in a gradual manner encompassing two rounds of cell division, as well as cell positional and morphological changes. While it is known that the activity of the Hippo signaling pathway and the subcellular localization of its downstream effector YAP dictate lineage specific gene expression, the response of YAP to these dynamic cellular changes remains incompletely understood. Here we address these questions by quantitative live imaging of endogenously tagged YAP while simultaneously monitoring geometric cellular features and cell cycle progression throughout cell fate segregation. We apply a probabilistic model to our dynamic data, providing a quantitative characterization of the mutual effects of YAP and cellular relative exposed area, which has previously been shown to correlate with subcellular YAP localization in fixed samples. Additionally, we study how nuclear YAP levels are influenced by other factors, such as the decreasing pool of maternally provided YAP that is partitioned to daughter cells through cleavage divisions, cell cycle-associated nuclear volume changes, and a delay after divisions in adjusting YAP levels to new cell positions. Interestingly, we find that establishing low nuclear YAP levels required for the inner cell mass fate is largely achieved by passive cell cycle-associated mechanisms. Moreover, contrary to expectations, we find that mechanical perturbations that result in cell shape changes do not influence YAP localization in the embryo. Together our work identifies how various inputs are integrated over a dynamic developmental time course to shape the levels of a key molecular determinant of the first cell fate choice.
| S-EPMC11888467 | biostudies-literature
Project description:During the maternal-to-zygotic transition (MZT), maternal proteins in oocytes are degraded by the ubiquitin-proteasome system (UPS), and new proteins are synthesized from the zygotic genome. However, the specific mechanisms underlying the UPS at the MZT are not well understood. We identified a molecule named zygote-specific proteasome assembly chaperone (ZPAC) that is specifically expressed in mouse gonads, and expression of ZPAC was transiently increased at the mouse MZT. ZPAC formed a complex with Ump1 and associated with precursor forms of 20S proteasomes. Transcription of ZPAC genes was also under the control of an autoregulatory feedback mechanism for the compensation of reduced proteasome activity similar to Ump1 and 20S proteasome subunit gene expression. Knockdown of ZPAC in early embryos caused a significant reduction of proteasome activity and decrease in Ump1 and mature proteasomes, leading to accumulation of proteins that need to be degraded at the MZT and early developmental arrest. Therefore, a unique proteasome assembly pathway mediated by ZPAC is important for progression of the mouse MZT.
| S-EPMC3575651 | biostudies-literature
Project description:Exposure to inorganic arsenic through drinking water is widespread and has been linked to many chronic diseases, including cardiovascular disease. Arsenic exposure has been shown to alter hypertrophic signaling in the adult heart, as well as in utero offspring development. However, the effect of arsenic on maternal cardiac remodeling during pregnancy has not been studied. As such, there is a need to understand how environmental exposure contributes to adverse pregnancy-related cardiovascular events. This study seeks to understand the impact of trivalent inorganic arsenic exposure during gestation on maternal cardiac remodeling in late pregnancy, as well as offspring outcomes. C57BL/6 J mice were exposed to 0 (control), 100 or 1000 μg/L sodium arsenite (NaAsO2) beginning at embryonic day (E) 2.5 and continuing through E17.5. Maternal heart function and size were assessed via transthoracic echocardiography, gravimetric measurement, and histology. Transcript levels of hypertrophic markers were probed via qRT-PCR and confirmed by western blot. Offspring outcomes were assessed through echocardiography and gravimetric measurement. We found that maternal heart size was smaller and transcript levels of Esr1 (estrogen receptor alpha), Pgrmc1 (progesterone receptor membrane component 1) and Pgrmc2 (progesterone receptor membrane component 2) reduced during late pregnancy with exposure to 1000 μg/L iAs vs. non-exposed pregnant controls. Both 100 and 1000 μg/L iAs also reduced transcription of Nppa (atrial natriuretic peptide). Akt protein expression was also significantly reduced after 1000 μg/L iAs exposure in the maternal heart with no change in activating phosphorylation. This significant abrogation of maternal cardiac hypertrophy suggests that arsenic exposure during pregnancy can potentially contribute to cardiovascular disease. Taken together, our findings further underscore the importance of reducing arsenic exposure during pregnancy and indicate that more research is needed to assess the impact of arsenic and other environmental exposures on the maternal heart and adverse pregnancy events.
| S-EPMC10922692 | biostudies-literature
Project description:BackgroundEmbryonic and fetal exposure to maternal obesity causes several maladaptive morphological and epigenetic changes in exposed offspring. The timing of these events is unclear, but changes can be observed even after a short exposure to maternal obesity around the time of conception. The hypothesis of this work is that maternal obesity influences the ovine preimplantation conceptus early in pregnancy, and this exposure will affect gene expression in embryonic and extraembryonic tissues.ResultsObese and lean ewe groups were established by overfeeding or normal feeding, respectively. Ewes were then bred to genetically similar rams. Conceptuses were collected at day 14 of gestation. Morphological assessments were made, conceptuses were sexed by genomic PCR analysis, and samples underwent RNA-sequencing analysis. While no obvious morphological differences existed between conceptuses, differentially expressed genes (≥ 2-fold; ≥ 0.2 RPKM; ≤ 0.05 FDR) were detected based on maternal obesity exposure (n = 21). Also, differential effects of maternal obesity were noted on each conceptus sex (n = 347). A large portion of differentially expressed genes were associated with embryogenesis and placental development.ConclusionsFindings reveal that the preimplantation ovine conceptus genome responds to maternal obesity in a sex-dependent manner. The sexual dimorphism in response to the maternal environment coupled with changes in placental gene expression may explain aberrations in phenotype observed in offspring derived from obese females.
| S-EPMC6180665 | biostudies-literature