Our findings indicate that prenatal ethanol exposure alters 5-HT(1A) and 5-HT(2A) receptor function in adulthood and does so in a sex-specific manner. These findings have important implications for altered hormonal and behavioral responsiveness observed in ethanol-exposed animals.

In recent decades, marine mammal populations living in highly polluted areas have experienced incidences of low reproductive success, developmental abnormalities and disease outbreaks. In many of these cases, environmental contaminants were suspected as causal or contributing factors. However, demonstrating a mechanistic link between contaminant exposure and effect in marine mammal populations has proven challenging. Consequently, the development and application of relatively noninvasive biomarkers represents a potentially valuable means of monitoring wildlife populations exposed to elevated levels of contaminants. One touted biomarker is vitamin A (retinol), a "dietary hormone" whose metabolites are required for reproduction, growth, development, immune function, vision and epithelial maintenance. Laboratory studies have shown that many contaminants, including polychlorinated biphenyls (PCBs), polychlorinated dibenzo-para-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), can disrupt vitamin A physiology and alter the distribution of its essential metabolites. Field studies suggest that complex environmental mixtures of these chemicals can also interfere with vitamin A dynamics in free-ranging marine mammals and other fish-eating wildlife. However, circulatory retinol, which is the least invasive measurement of vitamin A status, appears to have variable responses to contaminant exposure. In addition, "normal" circulatory retinol levels have not yet been described for most wildlife species, and not enough is known about the natural physiological events that can alter these concentrations. Confounding factors must therefore be characterized before retinoids can be used as an effective indicator of adverse health effects in marine mammals exposed to elevated levels of environmental contaminants.

Abstract-Marine mammals can bioaccumulate high concentrations of lipophilic environmental contaminants, such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-para-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs), through the diet. Both laboratory and wildlife studies have shown that these persistent chemicals can disrupt the regulation of vitamin A (retinol), a dietary hormone required for immune function, reproduction, growth, and development. To determine whether environmental contaminants affect the circulatory vitamin A dynamics of free-ranging harbor seals (Phoca vitulina), we live-captured 61 pups from British Columbia, Canada, and Washington State, USA, and obtained blood and blubber biopsy samples. Harbor seal pups from Washington State were six times more contaminated with total PCBs than pups from British Columbia and had significantly lower circulatory retinol levels. However, when data were corrected for differences in nursing status and analyzed as ungrouped sets of data, circulatory retinol levels were positively correlated with contaminant levels in the blubber of nonnursing pups. This increase in retinol may have resulted from a mobilization of liver vitamin A stores into circulation following exposure to milkderived contaminants; this has been observed in laboratory animals exposed experimentally. The contaminant-related disruption of vitamin A dynamics observed in our study occurs at a time when vitamin A is required for growth and development.

Although vitamin A (retinol) levels are highly regulated within individual organisms, natural (e.g., age, sex, disease) and anthropogenic (e.g., environmental contaminants) factors can affect the dynamics of this essential nutrient. In this study, we examined developmental changes in the circulatory vitamin A system of free-ranging harbour seal (Phoca vitulina) pups by collecting serial blood samples from healthy known-age animals throughout their nursing period. While harbour seal pups were born with relatively low levels of circulatory retinol (144.4 ± 13.9 µg/L), nursing animals more than doubled these levels within 2 days (385.0 ± 46.9 µg/L), and levels continued to rise more gradually until weaning (431.0 ± 35.8 µg/L). Animals that were not nursing, such as orphaned (184.4 ± 34.2 µg/L), fasted (347.0 ± 14.4 µg/L), and weaned (204.5 ± 38.5 µg/L) pups, had significantly lower circulatory retinol levels. Despite the developmental changes observed in total retinol, the concentration of retinol bound by its transport proteins, retinol binding protein and transthyretin, remained relatively constant throughout the nursing period. This suggests that, like most mammals, the delivery of retinol to target tissues is highly regulated in harbour seal pups. Furthermore, the high concentrations of circulatory retinol observed in harbour seal pups may serve to saturate transport proteins, ensuring a steady delivery of vitamin A to target tissues during a period of potentially variable supply. Understanding how natural factors affect circulatory retinol and its transport proteins is an important facet of assessing the impact of environmental contaminants on vitamin A dynamics in marine mammals.