Prenatal Exposure to DEHP Affects Spermatogenesis and Sperm DNA Methylation in a Strain-Dependent Manner.

Di-(2-ethylhexyl)phtalate (DEHP) is a plasticizer with endocrine disrupting properties found ubiquitously in the environment and altering reproduction in rodents. Here we investigated the impact of prenatal exposure to DEHP on spermatogenesis and DNA sperm methylation in two distinct, selected, and sequenced mice strains. FVB/N and C57BL/6J mice were orally exposed to 300 mg/kg/day of DEHP from gestation day 9 to 19. Prenatal DEHP exposure significantly decreased spermatogenesis in C57BL/6J (fold-change = 0.6, p-value = 8.7*10-4), but not in FVB/N (fold-change = 1, p-value = 0.9). The number of differentially methylated regions (DMRs) by DEHP-exposure across the entire genome showed increased hyper- and decreased hypo-methylation in C57BL/6J compared to FVB/N. At the promoter level, three important subsets of genes were massively affected. Promoters of vomeronasal and olfactory receptors coding genes globally followed the same trend, more pronounced in the C57BL/6J strain, of being hyper-methylated in DEHP related conditions. In contrast, a large set of micro-RNAs were hypo-methylated, with a trend more pronounced in the FVB/N strain. We additionally analyze both the presence of functional genetic variations within genes that were associated with the detected DMRs and that could be involved in spermatogenesis, and DMRs related with the DEHP exposure that affected both strains in an opposite manner. The major finding in this study indicates that prenatal exposure to DEHP can decrease spermatogenesis in a strain-dependent manner and affects sperm DNA methylation in promoters of large sets of genes putatively involved in both sperm chemotaxis and post-transcriptional regulatory mechanisms

Applied Solutions for Water Resource Challenges: Floods, Contamination and Upland Water Storage

poster abstractThe Center for Earth and Environmental Science, an IUPUI Signature Center, is working on a series of water resources problems and creating solutions. A series of collaborative projects are underway with the HUD, FEMA, the Office of Community and Rural Affairs, the United States Geological Survey, the Indiana State Department of Agriculture, and an international corporate partner in Berlin, KompetenzZentrum Wasser Berlin. Flood Erosion Hazard Program CEES, the USGS, and Polis are working with HUD and the Office of Community and Rural Affairs, though the Indiana Silver Jackets, to create tools for the State of Indiana to incorporate flood erosion hazard risk assessments into community planning. Flooding remains the most costly natural hazard in the US and Indiana. Flood losses continue to rise despite billions of dollars in mitigation. The causes are complex and related to land use, infrastructure design and climate change. Following the June 2008 floods in Indiana, 39 counties were listed as Federal disaster areas. In early 2005, 90% of Indiana counties were declared federal disaster areas after heavy rains fell on saturated soil. There have been seven major regional flooding events since the “Great flood of 1913”. The frequency of large floods appears to be increasing. Four of the eight major floods have occurred since 1982 and the last two occurred in 2005 and 2008. From 1998 through 2007, total insured flood losses in Indiana exceeded $39.8 million. While more restricted in area than the floods of 2008; record flooding occurred again throughout central and southern Indiana in early 2011 following heavy rains in February and March. Traditional flood protection usually consists of three components: flood control reservoirs, urban levees/floodwalls, and agricultural levees. These traditional flood protection methods are focused on one aspect of flooding – inundation. However, the largest single source of flood losses, both in terms of cost and number of affected persons, is damage to transportation infrastructure. Fluvial erosion is a principal cause of this damage. This significant flood-related natural hazard – the “fluvial erosion hazard” (FEH) – is not a specific component of State and local mitigation programs. This project aims to generate the tools for inclusion of FEH into statewide and local community planning. Aquisafe II - Performance Analysis of Selected Mitigation Systems Used to Attenuate Non-Point Source Agricultural Pollution Aquisafe is an international research collaboration with Veolia Environment based in Paris, their corporate partner in Berlin (KompetenzZentrum Wasser – Berlin Center of Competence for Water), the German Federal Environmental Agency, German university partners, and French quasi-governmental agencies in Brittany, France. The project goals are to create new mitigation systems to capture and treat polluted agricultural water running off farm fields prior to flowing into area streams, especially those used for drinking water supplies. The contaminants of specific concern are nutrients (nitrogen and phosphorus) and pesticides (atrazine – a corn-herbicide with potential endocrine disrupting effects). We are testing 2-stage, constructed wetlands in Indianapolis, Indiana and Brittany, France that have been designed to intercept and convert contaminants to harmless compounds. Site designs are guided by laboratory technical scale experiments conducted in Berlin that identified the hydrologic retention times and suitable sources of organic carbon necessary for mitigating contaminants. Construction of the experimental systems will begin in April in the Eagle Creek Watershed in cooperation with a private farmer with initial results expected this summer

Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10−8, 5.18 × 10−7 and 1.25 × 10−9, respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology

The biological basis and clinical significance of hormonal imprinting, an epigenetic process

The biological phenomenon, hormonal imprinting, was named and defined by us (Biol Rev, 1980, 55, 47-63) 30 years ago, after many experimental works and observations. Later, similar phenomena were also named to epigenetic imprinting or metabolic imprinting. In the case of hormonal imprinting, the first encounter between a hormone and its developing target cell receptor—usually at the perinatal period—determines the normal receptor-hormone connection for life. However, in this period, molecules similar to the target hormone (members of the same hormone family, synthetic drugs, environmental pollutants, etc), which are also able to bind to the receptor, provoke faulty imprinting also with lifelong—receptorial, behavioral, etc.,—consequences. Faulty hormonal imprinting could also be provoked later in life in continuously dividing cells and in the brain. Faulty hormonal imprinting is a disturbance of gene methylation pattern, which is epigenenetically inherited to the further generations (transgenerational imprinting). The absence of the normal or the presence of false hormonal imprinting predispose to or manifested in different diseases (e.g., malignant tumors, metabolic syndrome) long after the time of imprinting or in the progenies