Polychlorinated biphenyls (PCBs) alter DNA methylation and genomic integrity of sheep fetal cells in a simplified in vitro model of pregnancy exposure

Polychlorinated biphenyls (PCBs) are persistent organic pollutants ubiquitously detectable in the environment and in the food chain. Prenatal exposure to PCBs negatively affects fetal development and produces long-term detrimental effects on child health. The present study sought to evaluate the cytotoxic and genotoxic effects of chronic PCB exposure on fetal cells during pregnancy. To this aim, sheep embryonic fibroblasts (SEF) and amniocytes (SA) were cultured in vitro in the presence of low doses of PCBs for a period of 120 days, comparable to the full term of ovine pregnancy. Cellular proliferation rates, global DNA methylation, chromosome integrity, and markers of DNA damage were evaluated at different time points. Moreover, SEF treated with PCBs for 60 days were left untreated for one further month and then examined in order to evaluate the reversibility of PCB-induced epigenetic defects. PCB-treated SEF were more sensitive than SA treated with PCBs, in terms of low cell proliferation, and increased DNA damage and global DNA methylation, which were still detectable after interruption of PCB treatment. These data indicate that chronic exposure of fetal cells to PCBs causes permanent genomic and epigenetic instability, which may influence both prenatal and post-natal growth up to adulthood. Our in vitro model offer a simple and controlled means of studying the effects of different contaminants on fetal cells - one that could set the stage for targeted in vivo studies

The DNA cytosine methylome revealed two methylation motifs in the upstream regions of genes related to morphological and physiological differentiation in Streptomyces coelicolor A(3)2 M145

DNA methylation is an epigenetic modification detected in both prokaryotic and eukaryotic genomic DNAs. In bacteria, the importance of 5-methylcytosine (m5C) in gene expression has been less investigated than in eukaryotic systems. Through dot-blot analysis employing m5C antibodies against chromosomal DNA, we have previously demonstrated that m5C influences the differentiation of Streptomyces coelicolor A(3)2 M145 in solid sporulating and liquid non-sporulating complex media. Here, we mapped the methylated cytosines of the M145 strain growing in the defined Maltose Glutamate (MG) liquid medium. Sequencing of the M145 genome after bisulfite treatment (BS-sequencing) evidenced 3360 methylated cytosines and the two methylation motifs, GGCmCGG and GCCmCG, in the upstream regions of 321 genes. Besides, the role of cytosine methylation was investigated using the hypo-methylating agent 5'-aza-2'-deoxycytidine (5-aza-dC) in S. coelicolor cultures, demonstrating that m5C affects both growth and antibiotic biosynthesis. Finally, quantitative reverse-transcription polymerase-chain-reaction (RT-qPCR) analysis of genes containing the methylation motifs in the upstream regions showed that 5-aza-dC treatment influenced their transcriptional levels and those of the regulatory genes for two antibiotics. To the best of our knowledge, this is the first study that reports the cytosine methylome of S. coelicolor M145, supporting the crucial role ascribed to cytosine methylation in controlling bacterial gene expression

Effects of advanced paternal age on trajectories of social behavior in offspring

Our study is the first investigation of the effects of advanced paternal age (APA) on the developmental trajectory of social behavior in rodent offspring. Given the strong epidemiological association between APA and sexually dimorphic neurodevelopmental disorders that are characterized by abnormalities in social behavior (autism, schizophrenia), we assessed sociability in male and female inbred mice (C57BL/6J) across postnatal development (N=104) in relation to paternal age. We found differences in early social behavior in both male and female offspring of older breeders, with differences in this social domain persisting into adulthood in males only. We showed that these social deficits were not present in the fathers of these offspring, confirming a de novo origin of an altered social trajectory in the offspring generation. Our results, highly novel in rodent research, support the epidemiological observations in humans and provide evidence for a causal link between APA, age-related changes in the paternal sperm DNA and neurodevelopmental disorders in their offspring

Apple polyphenols in human and animal health*

Apples contain substantial amounts of polyphenols, and diverse phenolics mainly flavonoids and phenolic acids, have been identified in their flesh and skins. This work aimed to analyze the overall landscape of the research literature published to date on apple phenolic compounds in the context of human and animal health. The Web of Science Core Collection electronic database was queried with (apple* polyphenol*) AND (health* OR illness* OR disease* OR medic* OR pharma*) to identify relevant papers covering these words and their derivatives in the titles, abstracts, and keywords. The resulted 890 papers were bibliometrically analyzed. The VOSviewer software was utilized to produce term maps that illustrate how the frequent phrases fared in terms of publication and citation data. The apple polyphenol papers received global contributions, particularly from China, Italy, the United States, Spain, and Germany. Examples of frequently mentioned chemicals/chemical classes are quercetin, anthocyanin, catechin, epicatechin, and flavonol, while examples of frequently mentioned medical conditions are cardiovascular disease, atherosclerosis, diabetes, Alzheimers disease, and obesity. The potential health benefits of apple polyphenols on humans and animals are diverse and warrant further study.Authors acknowledge the support from The National Centre for Research and Development (NCBR) of Poland (project number POIR.01.01.01-00-0593/18).info:eu-repo/semantics/publishedVersio