Assessing effects of environmental chemicals on neuroendocrine systems: potential mechanisms and functional outcomes.

Environmental pollutants encompass a vast array of compounds. Most studies in birds have focused on toxicological effects, with little attention to non-lethal effects. Consequently, it has proven difficult to assess potential risk associated with exposure to endocrine disrupting chemicals (EDCs). Assessing potential adverse effects due to exposure is further complicated by the great variation that occurs across avian species. These include variations in reproductive strategies, life span, sexual differentiation, and migration. Differences in reproductive strategies, particularly in the developmental patterns and mechanisms for precocial and altricial chicks, predispose birds to wide variations in response to steroids and steroid-like EDCs. We have investigated the effects of EDCs in precocial birds including Japanese quail (Coturnix japonica) and mallard ducks (Anas platyrhynchos) as well as in wild altricial songbirds. Studies in Japanese quail characterized endogenous steroid hormone changes during development and have demonstrated that the developing embryo uses the yolk as a 'steroid hormone depot'. It appears that actual embryonic exposure is quantitatively lower than indicated by the treatment in egg injections and that the true amount of compound necessary for bioactivity may be quite low relative to the actual dosage delivered. Additionally, embryonic exposure to specific EDCs adversely affected sexual differentiation in quail, especially impacting male sexual behavior as well as neural systems, immune response, and thyroid hormones. Many of these studies considered single compounds; however, wild birds are exposed to complex mixtures and multiple compounds. We tested complex mixtures of polychlorinated biphenyls (PCBs) at concentrations that bracketed those found in eggs in contaminated regions. Results indicated that the predictive value of the toxic equivalency (TEQ), based on comparative activation of the aryl hydrocarbon receptor (AhR) relative to dioxin was not as accurate as expected. We discuss the potential of developing an endocrine disruption index (EDI) to bridge the inconsistencies observed between responses predicted by the TEQ and those observed in vivo following exposure to EDCs. Further, we will discuss how an EDI would complement the adverse outcome pathways analyses to consider the range of effects of endocrine disruptors in birds.

Ottinger MA ，Carro T ，Bohannon M ，Baltos L ，Marcell AM ，McKernan M ，Dean KM ，Lavoie E ，Abdelnabi M ... -  《-》

Neuroendocrine and behavioral implications of endocrine disrupting chemicals in quail.

Studies in our laboratory have focused on endocrine, neuroendocrine, and behavioral components of reproduction in the Japanese quail. These studies considered various stages in the life cycle, including embryonic development, sexual maturation, adult reproductive function, and aging. A major focus of our research has been the role of neuroendocrine systems that appear to synchronize both endocrine and behavioral responses. These studies provide the basis for our more recent research on the impact of endocrine disrupting chemicals (EDCs) on reproductive function in the Japanese quail. These endocrine active chemicals include pesticides, herbicides, industrial products, and plant phytoestrogens. Many of these chemicals appear to mimic vertebrate steroids, often by interacting with steroid receptors. However, most EDCs have relatively weak biological activity compared to native steroid hormones. Therefore, it becomes important to understand the mode and mechanism of action of classes of these chemicals and sensitive stages in the life history of various species. Precocial birds, such as the Japanese quail, are likely to be sensitive to EDC effects during embryonic development, because sexual differentiation occurs during this period. Accordingly, adult quail may be less impacted by EDC exposure. Because there are a great many data available on normal development and reproductive function in this species, the Japanese quail provides an excellent model for examining the effects of EDCs. Thus, we have begun studies using a Japanese quail model system to study the effects of EDCs on reproductive endocrine and behavioral responses. In this review, we have two goals: first, to provide a summary of reproductive development and sexual differentiation in intact Japanese quail embryos, including ontogenetic patterns in steroid hormones in the embryonic and maturing quail. Second, we discuss some recent data from experiments in our laboratory in which EDCs have been tested in Japanese quail. The Japanese quail provides an excellent avian model for testing EDCs because this species has well-characterized reproductive endocrine and behavioral responses. Considerable research has been conducted in quail in which the effects of embryonic steroid exposure have been studied relative to reproductive behavior. Moreover, developmental processes have been studied extensively and include investigations of the reproductive axis, thyroid system, and stress and immune responses. We have conducted a number of studies, which have considered long-term neuroendocrine consequences as well as behavioral responses to steroids. Some of these studies have specifically tested the effects of embryonic steroid exposure on later reproductive function in a multigenerational context. A multigenerational exposure provides a basis for understanding potential exposure scenarios in the field. In addition, potential routes of exposure to EDCs for avian species are being considered, as well as differential effects due to stage of the life cycle at exposure to an EDC. The studies in our laboratory have used both diet and egg injection as modes of exposure for Japanese quail. In this way, birds were exposed to a specific dose of an EDC at a selected stage in development by injection. Alternatively, dietary exposure appears to be a primary route of exposure; therefore experimental exposure through the diet mimics potential field situations. Thus, experiments should consider a number of aspects of exposure when attempting to replicate field exposures to EDCs.

Ottinger MA ，Abdelnabi MA ，Henry P ，McGary S ，Thompson N ，Wu JM ... -  《HORMONES AND BEHAVIOR》

Neuroendocrine impacts of endocrine-disrupting chemicals in birds: life stage and species sensitivities.

Ottinger MA ，Dean KM 《-》

An overview of dioxin-like compounds, PCB, and pesticide exposures associated with sexual differentiation of neuroendocrine systems, fluctuating asymmetry, and behavioral effects in birds.

Ottinger MA ，Lavoie ET ，Abdelnabi M ，Quinn MJ Jr ，Marcell A ，Dean K ... -  《-》

Consequences of endocrine disrupting chemicals on reproductive endocrine function in birds: establishing reliable end points of exposure.

Ottinger MA ，Quinn MJ Jr ，Lavoie E ，Abdelnabi MA ，Thompson N ，Hazelton JL ，Wu JM ，Beavers J ，Jaber M ... -  《DOMESTIC ANIMAL ENDOCRINOLOGY》