Browsing by Subject "PCBs"
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Item An integrative analysis of the multi- and transgenerational effects of endocrine-disrupting chemicals on behavior and neurobiology(2018-05) Krishnan, Krittika; Gore, Andrea C., 1964-; Crews, David P; Hofmann, Hans A; Champagne, Frances AEndocrine-disrupting chemicals (EDCs) are ubiquitous environmental pollutants that are known to interfere with hormone action. Exposure to EDCs during hormone-sensitive periods of prenatal development can result in disease and dysfunction later in life. Furthermore, EDC effects have been reported in individuals several generations removed from the initial exposure. In this dissertation, I investigated the effects of preconceptional (F2 germ cell) exposure to EDCs, and the potential mechanisms by which these effects are transmitted transgenerationally (F3 generation). Two EDCs, a weakly estrogenic polychlorinated biphenyl (PCB) mixture and an anti-androgenic fungicide vinclozolin (VIN), were used in this dissertation to understand the impact of chemicals with differential mechnisms of action. We hypothesized that these EDCs would alter the behavioral, physiological and neuromolecular phenotype of adult F2 and F3 individuals in a sex and lineage specific manner. The results from the first study in this dissertation indicates that F2 males descended from the paternal lineage were most vulnerable to PCB exposure, as evidenced by altered serum hormone levels, number and acoustic properties of ultrasonic vocalizations (USVs) and male sexual behavior. To determine if EDCs affected the underlying neuromolecular phenotype of these F2 males, we assessed the expression of candidate genes in the medial preoptic area (POA) and ventromedial nucleus (VMN) of the hypothalamus. These regions are both hormone-sensitive and involved in the regulation of reproductive behaviors. These results did not parallel our behavioral findings from the previous chapter, since F2 males descended from the paternal lineage were most vulnerable to VIN exposure. Finally, we investigated whether ancestral EDC exposure, in combination with EDC-altered F2 maternal care, altered the anxiety phenotype of the F3 offspring. F2 individuals’ maternal care toward their F3 offspring, and the F3 neonatal USVs were altered depending on the EDC and the lineage of descended. Adult anxiety behaviors were mostly unaltered. Taken together, the findings from these studies suggest that exposure to EDCs during critical periods of development can result in multi- and transgenerational effects on behavior, physiology and neurobiology in a lineage and sex dependent manner. These results have implications for human and wildlife reproductive health, and could inform interventions for EDC exposures in the near futureItem Endocrine disruptors and hormonally-sensitive windows across the life cycle of females(2023-04-21) Kunkel, Marcela Nicole; Gore, Andrea C., 1964-; Dominguez, Juan; Cormack, Lawrence; Guarraci, Fay AEndocrine-disrupting chemicals (EDCs) pose serious threats to women’s health. Deleterious effects of EDC exposure early development, particularly during hormonally-sensitive windows, are well documented in longitudinal studies, demonstrating that effects are often “hidden” until adulthood. However, exposures rarely occur once, and EDCs are not the only neuroendocrine challenge one faces over the life course. Interactions between EDC exposures and other stressors are less understood. The first two experimental chapters of this dissertation focused on perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic mixture well-established endocrine disruptors called polychlorinated biphenyls (PCBs), and peripubertal sociosexual stress using the sexual conspecific aggressive response (SCAR) model using a 2x2 design. These stressors were hypothesized to interact: SCAR was expected to exacerbate or “unmask” A1221 exposure effects in adult female rats. Experiments did not show any interactions between A1221 and SCAR, treatments exerted independent effects. In the first study, neither treatment appeared to elicit depressive-like behavioral phenotypes, but rats exposed to A1221 exhibited dexamethasone (dex) nonsuppression during a dexamethasone suppression test (DST). In the second study, SCAR exerted anxiolytic effects during open field testing. In this study, SCAR experience was paired with an odor cue, and when experimental animals were assessed for odor preference, rats that underwent SCAR tended to show a stronger preference for the odor cue. At euthanasia (~P85), there were no group differences in cytochrome c oxidase (COX) in the paraventricular nucleus (PVN) of the hypothalamus, basolateral amygdala (BLA), or ventrolateral area of the ventromedial nucleus of the hypothalamus (VMNvl), and A1221-exposed animals tended to have lower circulating corticosterone (CORT). Results suggested that, in female rats, SCAR does not elicit a stressed phenotype, perinatal A1221 exposure perturbs stress reactivity, and treatments are not associated with changes in metabolism in brain. The fourth chapter of this dissertation is a systematic literature review and meta-analysis that investigated whether EDC exposure predisposes pregnant women to peripartum depression (PPD). Pregnancy is another hormonally-sensitive window that is under researched. Results demonstrated that EDC exposures increase the odds of pregnant women developing PPD, and this is an understudied and emerging research question.Item Evaluating organic compound sorption to several materials to assess their potential as amendments to improve in-situ capping of contaminated sediments(2011-05) Dunlap, Patrick John; Reible, Danny D.; Liljestrand, HowardContaminated sediments represent a common environmental problem because they can sequester large quantities of contaminants which can remain long after the source of pollution has been removed. From the sediment these hazardous compounds are released into the sediment porewater where it can partition into organisms in the sediment and bioaccumulate up the food web; leading to an ecological and human health concern. The objective of this work is to investigate an emerging option in contaminated sediment remediation; specifically an option for in-situ treatment known as active capping. Conventional capping uses clean sediment or sands to separate contaminated sediment from overlying water and biota. Active capping is the use of a sorptive amendment to such a cap to improve its effectiveness. This work focuses on granular materials as direct amendments to conventional caps including; granular activated carbon (GAC), iron/palladium amended GAC, alumina pillared clay, rice husk char, and organically modified clays. All materials were investigated in batch sorption tests of benzene, chlorobenzene, and naphthalene in DI water. Additionally porewaters from three sites were extruded and the concentrations of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) were measured. At Manistique Harbor and Ottawa River PCBs were identified as the primary contaminant of concern while PAHs were the contaminant of concern at the Grand Calumet River. At these sites a solvent extraction method was used to analyze the sediment concentrations of the contaminants of concern. From the former batch tests activated carbon and a commercially available organoclay were chosen for further investigation. This includes PAHs in batch sorption tests using extruded sediment porewater to investigate matrix effects, and PCB sorption in distilled water.Item Phenotypes and mechanisms of epigenetic transgenerational inheritance due to prenatal exposure of endocrine disrupting chemicals(2018-05) Gillette, Ross; Crews, David; Gore, Andrea C; Atkinson, Nigel S; McCarrey, John RNearly all humans and animals carry a measurable body burden of endocrine disrupting chemicals (EDCs), which interfere with or alter endogenous hormone signaling and cause various disease phenotypes depending on their composition, dose, and period of exposure. Furthermore, EDCs impart deleterious phenotypes on multiple generations without subsequent exposure. The inheritance of diseased phenotypes is believed to be the result of heritable mutations to the epigenome (epimutations) within the germline. It is essential that we understand how EDC exposure affects mammals and that we identify the mechanisms responsible for inheritance. It is the goal of this dissertation to describe and test the phenotypes associated with the transgenerational inheritance of epimutations due to two representative but common categories of EDCs; estrogenic – polychlorinated biphenyls (PCBs) and anti-androgenic – vinclozolin. To achieve this, I used a multidisciplinary and systems biology approach across animal behavior, physiology, brain metabolism, neural gene expression, and genetic sequencing. Pregnant dams were injected with vinclozolin, PCBs, or a vehicle control during mid to late gestation. The resulting generation was bred to obtain the F2 and F3 generation without further exposure. To understand how a diseased past might interact with a troubled present, ancestral EDC exposure was challenged with chronic restrain stress (CRS) during puberty. Last, both male and female animals were subjected to treatment to determine how development and different hormonal milieus altered the outcome. I found that ancestral exposure to vinclozolin decreased anxiety behavior, increased body weight, and altered the metabolic capacity of brain nuclei involved in anxiety behaviors. Exposure to CRS often exacerbated these effects. Gene expression analysis within discrete nuclei of the brain identified neural proliferation factors, thermoregulatory genes, and epigenetic machinery was altered by ancestral vinclozolin exposure. Males and females differed in their response to ancestral vinclozolin exposure and CRS; the hippocampus is more vulnerable in females and the amygdala is more vulnerable in males. Prenatal PCB exposure increased body weight in males and females but only affected anxiety behavior in males. Last, direct and ancestral exposure to vinclozolin and PCBs caused epimutations in the germline and brain of males. Substantial over lap in the affected sites suggest a common mechanism of interaction between EDCs and the epigenome.