Biomedical subjects

Christy M Foran

Publications and source records attributed to Christy M Foran.

15 recordsLinked to original sources

PubMed2007

Influence of persistent contaminants and steroid hormones on glioblastoma cell growth.

Glioblastoma multiforme (GBM), a malignancy characterized by its rapid progression, presents a lower risk of occurrence in women during their reproductive years. Necrosis of brain tissue during tumor invasion releases free lipids, and therefore might release contaminants stored in phospholipid-rich neuronal tissue. This study assesses the growth response of two human glioblastoma cell lines, T98G and U138-MG, treated with environmental chemicals known or likely to persist within the brain. Persistent chlorinated pesticides, industrial contaminants, persistent perfluorinated chemicals, and steroid hormones were assayed over a range of concentrations. Although cytotoxic effects were seen in both T98G and U138-MG cells, proliferative responses occurred only in the T98G cell line. Dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and polychlorinated biphenyl (PCB) 153 were cytotoxic in both lines at 5000 nM. Perfluorodecanoic acid (PFDA), perfluorooctane sulfonate (PFOS), and testosterone stimulated proliferation in the T98G cells at 500, 1000, and 1000 nM, respectively. However, a perfluorinated salt (ammonium perfluorooctanoate; C8) and a weak androgen (dihydroepiandrosterone; DHEA) did not affect relative cell number in this GBM line, suggesting the proliferative effect is not through the activation of an androgen receptor. Exposure to environmental chemicals that result in a mitogenic response may increase the rate of glioblastoma tumor growth and result in the development of more aggressive forms of GBM tumors.

Brain Neoplasms↗

PubMed2006

Changes in the timing of reproduction following chronic exposure to ibuprofen in Japanese medaka, Oryzias latipes.

Effluents from wastewater treatment plants and untreated sewage constitute a low concentration but continuous source of pharmaceutical products to the aquatic environment. One such drug, ibuprofen, is a non-steroidal anti-inflammatory agent that primarily acts through inhibition of cyclooxygenase (COX) activity. Oryzias latipes (Japanese medaka) were exposed for 6 weeks via water to three concentrations of ibuprofen (1-100 microg/L nominal concentrations) and a water control. Reproductive parameters, including frequency of spawning, fecundity, egg size, and rate of fertilization, were measured for each pair of adult medaka following 6 weeks of exposure. Livers homogenates from exposed individuals were assayed for COX activity and whole individuals were histologically examined for tissue damage. Increasing exposure to ibuprofen significantly increased the number of eggs per reproductive event, but decreased the number of spawning events per week. Liver tissue collected from females had less variability in COX activity with increasing concentration of ibuprofen exposure, and tended to have elevated hepatosomatic indices. No pathological damage was evident the in the gills, livers and head kidneys of animals from the highest exposure group. The results of this experiment begin to show that exposure to chronic low levels of ibuprofen alter the pattern of reproduction and may produce sex-specific responses in teleosts.

Animals↗

PubMed2006

Influence of estuarine hypoxia on feeding and sound production by two sympatric pipefish species (Syngnathidae).

This research utilizes the acoustic behavior of two sympatric pipefish species to assess the impact of hypoxia on feeding. We collected northern, Syngnathus fuscus, and dusky pipefishes, Syngnathus floridae, from the relatively pristine Chincoteague Bay, Virginia, USA and audiovisually recorded behavior in the laboratory of fish held in normoxic (>5 mg/L O(2)) and hypoxic (2 and 1 mg/L O(2)) conditions. Both species produced high frequency ( approximately 0.9-1.4 kHz), short duration (3-22 msec) clicks. Feeding strikes were significantly correlated with both wet weight of ingested food and click production. Thus, sound production serves as an accurate measure of feeding activity. In hypoxic conditions, reduced food intake corresponded with decreased sound production. Significant declines in both behaviors were evident after 1 day and continued as long as hypoxic conditions were maintained. Interspecific differences in sensitivity were detected. Specifically, S. floridae showed a tendency to perform head snaps at the surface. S. fuscus exhibited a breakdown in the coupling of sound production with food intake in 2 mg/L O(2) with clicks produced in other contexts, particularly choking and food expulsion. Reductions in feeding will ultimately impact growth, health, and eventually reproduction as resources are devoted to survival instead of gamete production and courtship. This work suggests acoustic monitoring of field sites with adverse environmental conditions may reflect changes in feeding behavior in addition to population dispersal.

Analysis of Variance↗

PubMed2006

Differential parental nutrient allocation in two congeneric pipefish species (Syngnathidae: Syngnathus spp.).

Male seahorses and pipefishes of the family Syngnathidae are heralded for their unique brood pouch structures for incubating embryos. There are three general types of brood pouch with increasing complexity: simple ventral gluing, two pouch flaps and a completely sealed sac. The diversity of functional roles within a type in providing nutrition, aeration and protection to offspring is unknown. Here we reveal significant differences in parental nutrient allocation to embryos for two closely related, sympatric pipefishes with similar brood pouch structure. We document differences in embryo attachment, depletion of pouch fluid nutrients over development and egg nutrient partitioning between Syngnathus floridae and Syngnathus fuscus. In S. fuscus, females produce nutritionally poor eggs and the males implant developing embryos in the brood pouch adjacent to blood vessels. A female-biased breeding population was observed, supporting the hypothesis that the cost of male parental care is high in this species. The loose connection between eggs and brood pouch tissues and the appearance of undeveloped eggs and lipid droplets in the pouch of S. floridae males suggest this species utilizes nutrient-rich eggs produced by females as nurse eggs to supplement embryonic development. A balanced sex-ratio for S. floridae further supports more equal parental contribution. This comparison provides evidence of a decline in female gametic investment and reveals the rapid diversification of syngnathid brood pouch function. Our results indicate gross classification of brooding structures into one of the three general pouch types does not predict the energetic investment of males in parental care. But rather, physiological characterization of the relative investment by each sex to offspring is essential to understanding the functional significance of the brood pouch.

Animal Feed↗

PubMed2005

Relationship between ethinylestradiol-mediated changes in endocrine function and reproductive impairment in Japanese medaka (Oryzias latipes).

Many biochemical endpoints currently are used to describe endocrine function in fish; however, the sensitivity of these parameters as biomarkers of impaired reproduction or sexual development is not well understood. In the present study, adult Japanese medaka (Oryzias latipes) were assessed for reproductive output and endocrine function, including circulating steroid concentrations, ex vivo steroidogenesis from the gonads, aromatase activity, hepatic estrogen receptor (ER), and plasma vitellogenin (VTG) after exposure to 0, 0.2, 5, 500, and 2,000 ng/L of 17alpha-ethinylestradiol (EE) for 14 d. The EE altered these biochemical responses at various sites along the hypothalamus-pituitary-gonadal axis at concentrations as low as 0.2 ng/L, but it only depressed reproductive function at concentrations of 500 ng/L or greater. Offspring also had reduced ability to hatch at 500 ng/L of EE, but this concentration did not produce any other observed changes in development or sexual phenotype. The reproductive parameters correlated well with VTG, ER, and gonadosomatic index (GSI) in both sexes of adult medaka, which could be indicative of the ER-mediated mode of action for EE. Vitellogenin and ER were elevated at higher concentrations of EE in both sexes, whereas GSI was decreased. Overall, most biochemical endpoints were more sensitive than reproduction or development to exposure, indicating that reproductive function may be relatively protected.

Animals↗

PubMed2004

Evidence of gender-and tissue-specific promoter methylation and the potential for ethinylestradiol-induced changes in Japanese medaka (Oryzias latipes) estrogen receptor and aromatase genes.

In order to explore the potential of DNA methylation to serve as a biomarker of toxicity, thus establishing a link between exposure to environmental contaminants and physiologically significant changes in gene expression, tissue- and gender-specific methylation patterns in the promoter regions of estrogen receptor (ER) and aromatase genes of Japanese medaka (Oryzias latipes) were determined. Adult male and female medaka were exposed to either 0 or 500 ng/L 17 alpha-ethinylestradiol (EE) for 14d via a waterborne exposure. Livers, gonads, and brains were removed and genomic DNA was extracted. Samples of genomic DNA were then analyzed by bisulfite-mediated methylation-specific polymerase chain reaction (PCR) of an approximately 300-bp region containing suspected methylation sites from the two genes, amplified, cloned, and sequenced. ER protein content in exposed medaka was significantly induced in all male and female tissues compared to controls. Aromatase activity in exposed medaka was significantly increased in the male brain, testes, and female brain as compared to controls. The methylation changes described by these studies indicate the potential for anthropogenic alteration of the mechanisms controlling gene expression, as well as gender- and tissue-specific sensitivity. While methylation differences were not paralleled by changes in protein expression in this study, changes in methylation have the potential to impact the regulation of normal gene expression and these changes could be transmitted to offspring.

Amino Acid Sequence↗

PubMed2004

Reproductive assessment of Japanese medaka (Oryzias latipes) following a four-week fluoxetine (SSRI) exposure.

The occurrence of environmental pharmaceutical products has recently received considerable attention, but impacts on the aquatic environment are largely unknown. Fluoxetine is a widely prescribed antidepressant and acts physiologically as a selective serotonin reuptake inhibitor (SSRI). To determine its potential to disrupt teleost reproductive function, Japanese medaka (Oryzias latipes) were exposed to fluoxetine at aqueous nominal concentrations of 0, 0.1, 0.5, 1 and 5 microg/L for 4 weeks. The last 14 days of this exposure included a reproductive assessment in which no significant changes were observed in egg production, rate of fertilization and spawning, or hatching success of fertilized eggs. A low incidence (1.97-2.53%; 4.02-5.16-fold greater than controls) of developmental abnormalities was observed in offspring from all fluoxetine treatments. Adult gonadal somatic index, hepatic vitellogenin, and ex vivo gonadal steroidogenesis were also unaffected. Circulating plasma estradiol levels in females were significantly increased by 0.1 and 0.5 microg/L treatments. Our study provides novel information on fish biochemical, physiological, and reproduction responses to environmentally realistic fluoxetine concentrations.

Animals↗

PubMed2003

Aquatic ecotoxicology of fluoxetine.

Recent studies indicate that the pharmaceutical fluoxetine, a selective serotonin reuptake inhibitor, is discharged in municipal wastewater treatment plant effluents to surface waters. Few data on environmental fluoxetine exposure and hazard to aquatic life are currently available in the literature. Here, we summarize information on fluoxetine detection in surface waters and review research on single-species toxicity test, Japanese medaka (Oryzias latipes) reproduction and endocrine function, and freshwater mesocosm community responses to fluoxetine exposure. Based on results from our studies and calculations of expected introduction concentrations, we also provide a preliminary aquatic risk characterization for fluoxetine. If standard toxicity test responses and a hazard quotient risk characterization approach are solely considered, little risk of fluoxetine exposure may be expected to aquatic life. However, our findings indicate that: (1) the magnitude, duration and frequency of fluoxetine exposure in aquatic systems requires further investigation; (2) mechanistic toxicity of fluoxetine in non-target biota, including behavioral responses, are clearly not understood; and (3) an assessment of environmentally relevant fluoxetine concentrations is needed to characterize ecological community responses.

Animals↗

PubMed2003

Effects of cadmium on the reproductive axis of Japanese medaka (Oryzias latipes).

Cadmium (Cd) is a ubquitous element and a significant inorganic pollutant that has previously been found to bioaccumulate in reproductive organs of fish and disrupt important endocrine processes, especially those involved in synthesis, release and metabolism of hormones. Clearly, there is potential for reproductive effects in fish populations exposed to Cd, however, few studies have investigated the non-lethal consequences of Cd in fish. To this extent, adult male and female Japanese medaka were exposed to 0-10 ppb Cd for 7 weeks. Reproductive endpoints were monitored during weeks 6 and 7 of exposure and compared to physiological responses along the hypothalamus-pituitary-gonadal (HPG) axis, including plasma vitellogenin (VTG), hepatic estrogen receptor (ER), plasma steroids, gonadal-somatic indices (GSI), and gonadal steroid release. There were no observed effects on VTG and ER by long-term Cd exposure. However, gonadal steroid release was significantly decreased in males and females at all exposure concentrations and female plasma estradiol levels were significantly altered at concentrations higher than 5 ppb Cd. Overall, responses along the HPG axis were more sensitive to Cd exposure than the reproductive and developmental endpoints, which were not affected in this study, indicating that higher level impairment in fish might be relatively protected.

Animals↗

PubMed2003

Waterborne and sediment toxicity of fluoxetine to select organisms.

Ecological risk assessments of pharmaceuticals are currently difficult because little-to-no aquatic hazard and exposure information exists in the peer-reviewed literature for most therapeutics. Recently several studies have identified fluoxetine, a widely prescribed antidepressant, in municipal effluents. To evaluate the potential aquatic toxicity of fluoxetine, single species laboratory toxicity tests were performed to assess hazard to aquatic biota. Average LC(50) values for Ceriodaphnia dubia, Daphnia magna, and Pimephales promelas were 0.756 (234 microg/l), 2.65 (820 microg/l), and 2.28 microM (705 microg/l), respectively. Pseudokirchneriella subcapitata growth and C. dubia fecundity were decreased by 0.044 (14 microg/l) and 0.72 microM (223 microg/l) fluoxetine treatments, respectively. Oryias latipes survival was not affected by fluoxteine exposure up to a concentration of 28.9 microM (8.9 mg/l). An LC(50) of 15.2 mg/kg was estimated for Chironomus tentans. Hyalella azteca survival was not affected up to 43 mg/kg fluoxetine sediment exposure. Growth lowest observed effect concentrations for C. tentans and H. azteca were 1.3 and 5.6 mg/kg, respectively. Our findings indicate that lowest measured fluoxetine effect levels are an order of magnitude higher than highest reported municipal effluent concentrations.

Amphipoda↗

PubMed2003

Comparison of in vitro and in vivo bioassays for estrogenicity in effluent from North American municipal wastewater facilities.

Attempts to better understand causal factors affecting estrogenicity in municipal wastewater have primarily focused on analytical evaluation of specific chemical estrogens and the use of estrogen receptor (ER) based in vitro assays. To compare analytical,in vitro, and in vivo assays for estrogenicity, wastewater from four New York and one Texas municipal wastewater facilities was evaluated for estrogenic activity using the yeast estrogen screen assay (YES) and an in vivo fish vitellogenin (VTG) assay. Estrogenic activity, as measured by the YES assay, was observed in methanol and/or methylene chloride eluents from C18 extracts in two of the New York treatment facilities and the Texas facility. Estradiol equivalents for the YES assay data ranged from </=1 to 15 ng/l. Male Japanese medaka (Oryzias latipes) were then exposed for 7 days to solvent extracts from the New York-Red Hook facility and the Texas facility. Hepatic and plasma vitellogenin were induced in medaka after exposure to the methanol eluent from the New York facility, even though the YES assay indicated that both the methanol and methylene chloride eluents were estrogenic. Whereas an estrogenic response in the YES assay was only observed in the methanol eluent from the Texas facility, plasma VTG induction was observed in both the methanol and methylene chloride eluents. In vivo estrogenic activity was nearly 10-fold greater than YES activity indicating the presence of nonestrogen receptor ligands that elicit estrogenic effects in fish through indirect mechanisms. The sole use of in vitro assays to screen for estrogenicity may underestimate estrogenic potential of wastewater.

Animals↗

PubMed2003

In vivo effects of black cohosh and genistein on estrogenic activity and lipid peroxidation in Japanese Medaka (Oryzias latipes).

This study was designed to assay the estrogenic activities and the antioxidant potential of ethanol extracts from the herbal dietary supplement black cohosh (Cimicifuga racemosa) relative to the natural phytoestrogen genistein. The in vivo mechanisms of action of these two natural products have not been completely elucidated, and Japanese medaka (Oryzias latipes) provides a useful organism for initial in vivo screening of natural products. While both genistein and estradiol altered ovarian and testicular steroid release and decreased circulating testosterone levels in males, neither black cohosh total extract (75-30,000 ng/fish), cimiracemoside A, 25-O-methyl-cimigenoside, actein, nor 26-deoxy-actein caused any differences in estrogenic activity compared to control fish. To assess antioxidant potential, animals were treated with natural products then challenged with 2-acetylaminofluorene (2-AAF) to induce lipid peroxidation (LPO) in the liver. Neither the total ethanol extracts from black cohosh nor its individual components showed an inhibitory effect in 2-AAF induced LPO. However, genistein manifested potent antioxidative activity in the LPO assay, with similar potency to a high dose of á-tocopherol. In contrast to genistein, black cohosh did not exhibit traditional estrogenic effects nor significant in vivo anti-oxidant potential in this fish model system.

Journal Article↗

PubMed2002

Characterization of the estrogenic response to genistein in Japanese medaka (Oryzias latipes).

This study was designed to determine the estrogenic effect of the phytoestrogen genistein on several measures of endocrine function in adult Japanese medaka (Oryzias latipes) relative to 17-beta-estradiol. Adult animals of both sexes were exposed to 75, 750 and 30,000 ng/fish (average fish weight equals 0.26 g) of genistein by i.p. injection, with a positive control group treated with 300 ng/fish of 17-beta-estradiol, while a negative control group received a vehicle-only (corn oil) injection. Content of vitellogenin, the yolk glycoprotein made in the liver in response to estradiol stimulation, was measured using Western blots. Circulating estradiol and testosterone levels were measured using a steroid-enzyme immunosorbant assay. The ability of ovaries and testes to synthesize and release estradiol and testosterone was determined by ex vivo incubation of gonads with 25-hydroxycholesterol. Vitellogenin, while induced by 17-beta-estradiol, was not increased in the liver of individuals treated with genistein. In females, genistein treatment at 750 and 30,000 ng increased the estradiol production of ovaries more than the 17-beta-estradiol treatment. In males, genistein treatment resulted in decreased testosterone production from ex vivo testis and a comparable reduction in circulating testosterone level. The changes in vitellogenin, circulating steroids and ex vivo steroidogenesis in medaka in response to genistein are similar to that of 17-beta-estradiol. However, some endpoints are more sensitive to estradiol treatment (vitellogenin), while others are more sensitive to genistein (male testosterone and ovarian estrogenesis).

Animals↗

PubMed2002

Influence of parental and developmental cadmium exposure on endocrine and reproductive function in Japanese medaka (Oryzias latipes).

Cadmium (Cd) is a ubiquitous element and an important anthropogenic metal contaminant. A series of assays were modified or developed for Japanese medaka (Oryzias latipes), and used to compare the effects of Cd exposure on indicators of endocrine function in adult animals previously exposed in ovo or as hatchlings. Adults were raised either from eggs produced during a 2 week exposure to 0-10 microg/l Cd or from fry exposed for 2 weeks beginning 2 days after hatching. The reproductive capacity of the resulting adults was determined during a 2 week period during which half of the animals were re-exposed to Cd. Two week Cd exposure did not result in reproductive impairment despite producing some changes in circulating steroid concentration. In addition, 1 microg/l cadmium exposure in ovo elevated male hepatic vitellogenin (VTG) relative to controls. Hence, steroid parameters were a better biomarker of cadmium exposure than changes in VTG. However, reproductive impairment was not correlated to change in VTG or plasma steroids.

Abnormalities, Drug-Induced↗

PubMed2002

Transgenerational and developmental exposure of Japanese medaka (Oryzias latipes) to ethinylestradiol results in endocrine and reproductive differences in the response to ethinylestradiol as adults.

17alpha-Ethinylestradiol (EE), a synthetic estrogen found in birth control pills, has been detected in the effluent of municipal wastewater treatment plants in several countries. Because EE was designed to be extremely potent at the estrogen receptor (ER), environmental exposure to low concentrations has the potential to disrupt the development of normal endocrine and reproductive function when exposure occurs during critical periods in development. Japanese medaka, Oryzias latipes, were used to evaluate the effect of exposure to EE during development on adult reproduction and endocrine function and the sensitivity of these animals to estrogen exposure as adults. To determine if the response to exogenous estrogen stimulation was diminished or sensitized, adults resulting from the developmental exposure groups were reexposed to EE at respectively higher concentrations. Hatchling exposure produced no changes in adult vitellogenin (VTG) content in the liver or circulating steroid concentrations, nor was reproduction affected. Reexposure of these adults inhibited reproduction, increased hepatic VTG and ER, and increased estrogen concentration measured in male plasma. Parental exposure produced permanent changes in hepatic content of ER and VTG in the adults resulting from exposure during gametogenesis and was related to a diminished response of males to subsequent estrogen exposure. The potential for this transgenerational exposure to decrease the responsiveness of males to EE is supported by comparing the concentration-response curves for hepatic VTG and ER in males exposed in ovo and as hatchlings. Our results indicate that the relationship between biomarkers and estrogen exposure will be altered by the timing and frequency of exposure.

Abnormalities, Drug-Induced↗