Exposure to environmental contaminants and folic acid supplementation intergenerationally impact fetal skeleton development through the paternal lineage in a rat model.

Persistent organic pollutants (POPs) are ubiquitous in the environment, which is of concern since they are broadly toxic for wildlife and human health. It is generally accepted that maternal prenatal folic acid supplementation (FA) may beneficially impact offspring development, but it has been recently shown that the father's exposures also influence the health of his offspring. Bone is an endocrine organ essential for whole-body homeostasis and is susceptible to toxicants.

Early-Life Exposure to Environmental Contaminants Perturbs the Sperm Epigenome and Induces Negative Pregnancy Outcomes for Three Generations via the Paternal Lineage.

Due to the grasshopper effect, the Arctic food chain in Canada is contaminated with persistent organic pollutants (POPs) of industrial origin, including polychlorinated biphenyls and organochlorine pesticides. Exposure to POPs may be a contributor to the greater incidence of poor fetal growth, placental abnormalities, stillbirths, congenital defects and shortened lifespan in the Inuit population compared to non-Aboriginal Canadians. Although maternal exposure to POPs is well established to harm pregnancy outcomes, paternal transmission of the effects of POPs is a possibility that has not been well investigated.

Adipose Tissue Transcriptome Is Related to Pollutant Exposure in Polar Bear Mother-Cub Pairs from Svalbard, Norway.

Being at the food chain apex, polar bears () are highly contaminated with persistent organic pollutants (POPs). Females transfer POPs to their offspring through gestation and lactation; therefore, young cubs present higher POPs concentrations than their mothers. Recent studies suggest that POPs affect the lipid metabolism in female polar bears; however, the mechanisms and impact on their offspring remain unknown.

Beyond fertilisation: How the paternal environment influences future generations.

In light of the relatively ignored role of paternal influences on offspring development and increasing societal concerns regarding possible health consequences of chemical exposures, our team has addressed the overall hypothesis that environmentally-relevant levels of contaminants have long-lasting effects that are transmitted through the paternal lineage. This review focuses on our research examining the impact of developmental exposure to toxicants and nutrients on the phenotype and epigenome of the male and of his subsequent generations. This report is intended to encourage animal andrologists as well as the domestic animal production industry to increase their consideration of the sire's environment in the context of agricultural productivity.

Prenatal Exposure to Environmentally-Relevant Contaminants Perturbs Male Reproductive Parameters Across Multiple Generations that are Partially Protected by Folic Acid Supplementation.

The paternal environment is thought to influence sperm quality and future progeny may also be impacted. We hypothesized that prenatal exposure to environmentally-relevant contaminants impairs male reproduction, altering embryo gene expression over multiple generations. Folic acid (FA) can improve sperm quality and pregnancy outcomes, thus we further hypothesized that FA mitigates the contaminants.

Maternal folic acid supplementation does not counteract the deleterious impact of prenatal exposure to environmental pollutants on lipid homeostasis in male rat descendants.

Prenatal exposure to persistent organic pollutants (POPs) has been associated with the development of metabolic syndrome-related diseases in offspring. According to epidemiological studies, father's transmission of environmental effects in addition to mother's can influence offspring health. Moreover, maternal prenatal dietary folic acid (FA) may beneficially impact offspring health.

Inferring and modeling inheritance of differentially methylated changes across multiple generations.

High-throughput methylation sequencing enables genome-wide detection of differentially methylated sites (DMS) or regions (DMR). Increasing evidence suggests that treatment-induced DMS can be transmitted across generations, but the analysis of induced methylation changes across multiple generations is complicated by the lack of sound statistical methods to evaluate significance levels. Due to software design, DMS detection was usually made on each generation separately, thus disregarding stochastic effects expected when a large number of DMS is detected in each generation.

Histomorphologic Analysis of the Late-term Rat Fetus and Placenta.

Histological examination of the rat placenta and fetus is uncommon. Toxicological studies mainly rely on gross examination of the fetus and on fetal and placental weights. These are often insufficient to assess the fetal and placental toxicity of xenobiotics.

Histone deacetylase 9 regulates breast cancer cell proliferation and the response to histone deacetylase inhibitors.

Histone lysine acetylation is an epigenetic mark regulated by histone acetyltransferases and histone deacetylases (HDAC) which plays an important role in tumorigenesis. In this study, we observed a strong overexpression of class IIa HDAC9, at the mRNA and protein levels, in the most aggressive human breast cancer cell lines (i.e.

A Scalable Genome-Editing-Based Approach for Mapping Multiprotein Complexes in Human Cells.

Conventional affinity purification followed by mass spectrometry (AP-MS) analysis is a broadly applicable method used to decipher molecular interaction networks and infer protein function. However, it is sensitive to perturbations induced by ectopically overexpressed target proteins and does not reflect multilevel physiological regulation in response to diverse stimuli. Here, we developed an interface between genome editing and proteomics to isolate native protein complexes produced from their natural genomic contexts.

HDAC inhibition does not induce estrogen receptor in human triple-negative breast cancer cell lines and patient-derived xenografts.

Several publications have suggested that histone deacetylase inhibitors (HDACis) could reverse the repression of estrogen receptor alpha (ERα) in triple-negative breast cancer (TNBC) cell lines, leading to the induction of a functional protein. Using different HDACis, vorinostat, panobinostat, and abexinostat, we therefore investigated this hypothesis in various human TNBC cell lines and patient-derived xenografts (PDXs). We used three human TNBC cell lines and three PDXs.

Reptin and Pontin oligomerization and activity are modulated through histone H3 N-terminal tail interaction.

Pontin/RUVBL1 and Reptin/RUVBL2 are DNA-dependent ATPases involved in numerous cellular processes and are essential components of chromatin remodeling complexes and transcription factor assemblies. However, their existence as monomeric and oligomeric forms with differential activity in vivo reflects their versatility. Using a biochemical approach, we have studied the role of the nucleosome core particle and histone N-terminal tail modifications in the assembly and enzymatic activities of Reptin/Pontin.

Increased macroH2A1.1 expression correlates with poor survival of triple-negative breast cancer patients.

Purpose: Epithelial-Mesenchymal Transition (EMT) features appear to be key events in development and progression of breast cancer. Epigenetic modifications contribute to the establishment and maintenance of cancer subclasses, as well as to the EMT process. Whether histone variants contribute to these transformations is not known.

DNA dynamics during early double-strand break processing revealed by non-intrusive imaging of living cells.

Chromosome breakage is a major threat to genome integrity. The most accurate way to repair DNA double strand breaks (DSB) is homologous recombination (HR) with an intact copy of the broken locus. Mobility of the broken DNA has been seen to increase during the search for a donor copy.

TIP48/Reptin and H2A.Z requirement for initiating chromatin remodeling in estrogen-activated transcription.

Histone variants, including histone H2A.Z, are incorporated into specific genomic sites and participate in transcription regulation. The role of H2A.

Activation of p21 by HDAC inhibitors requires acetylation of H2A.Z.

Differential positioning of the histone variant H2A.Z in a p53 dependent manner was shown to regulate p21 transcription. Whether H2A.

Oct1 is required for mTOR-induced G1 cell cycle arrest via the control of p27(Kip1) expression.

Oct1 is a ubiquitously expressed transcription factor that is induced in response to DNA damage to modulate gene expression. Herein, Oct1 deficient mouse embryonic fibroblasts were used as a model to study the importance of Oct1 in cellular stress response. Cells lacking Oct1 kept proliferating and bypassed the G(1) cell cycle arrest induced by glucose or amino acid starvation.

Oct1 regulates trophoblast development during early mouse embryogenesis.

Oct1 (Pou2f1) is a transcription factor of the POU-homeodomain family that is unique in being ubiquitously expressed in both embryonic and adult mouse tissues. Although its expression profile suggests a crucial role in multiple regions of the developing organism, the only essential function demonstrated so far has been the regulation of cellular response to oxidative and metabolic stress. Here, we describe a loss-of-function mouse model for Oct1 that causes early embryonic lethality, with Oct1-null embryos failing to develop beyond the early streak stage.

Cell cycle and anti-estrogen effects synergize to regulate cell proliferation and ER target gene expression.

Antiestrogens are designed to antagonize hormone induced proliferation and ERalpha target gene expression in mammary tumor cells. Commonly used drugs such as OH-Tamoxifen and ICI 182780 (Fulvestrant) block cell cycle progression in G0/G1. Inversely, the effect of cell cycle stage on ER regulated gene expression has not been tested directly.

The role of histone modifications and variants in regulating gene expression in breast cancer.

The role of epigenetic phenomena in cancer biology is increasingly being recognized. Here we focus on the mechanisms and enzymes involved in regulating histone methylation and acetylation, and the modulation of histone variant expression and deposition. Implications of these epigenetic marks for tumor development, progression and invasiveness are discussed with a particular emphasis on breast cancer progression.