Differentiation of Brain and Reproductive Organs in Birds : Effects of Environmental Contaminants

Abstract: The first objective of this thesis was to investigate effects of endocrine disruptors on the developing brain and gonads of bird embryos. The substances studied were the insecticide methoxychlor, and nine UV-filters (3-benzylidene camphor (3BC), 4 methyl benzylidene camphor (4MBC), benzophenone (BP) 1,2 and 3, 4 hydroxy benzophenone (4 HB), 4 dihydroxy benzophenone (4DHB), benzyl salicylate (BS), and ethyl-4-aminobenzoate Et-PABA)), commonly used in cosmetic products. Some of these substances have no estrogenic effect in vitro, but have been shown to be estrogenic in vivo. The PCB-mixture Clophen A50 is a well-known inducer of biotransformation enzymes and was co-administered with methoxychlor and the UV-filters 3BC and 4MBC. Exposure to 3BC or 4MBC caused ovotestis formation and malformations of the Müllerian ducts in Japanese quail embryos. Co-exposure to one of these compounds and Clophen A50 enhanced the effects, indicating that Clophen A50 potentiates the effects of the UV-filters. Embryonic co-exposure to Clophen A50 and methoxychlor caused a disturbed male sexual behaviour. The metabolites of methoxychlor are estrogen receptor (ER)α-selective, which indicates that the effects on behaviour following embryonic treatment were mediated by ERα. Another objective in this thesis was to localize estrogen receptors (ERs) in the brain of adult and embryonic Japanese quail. The ER localization provides a basis for mechanistic studies on effects of endocrine disruptors, by the identification of estrogen-responsive areas in the brain. We found that ERβ, not previously implicated in sex-differentiation of the brain, was the only ER-subtype present in a sexually dimorphic brain area during differentiation. In conclusion, the estrogenic effects of 3BC, 4MBC and methoxychlor were increased by co-exposure to PCB. These results raise concern since many wildlife species, as well as humans, carry large body burdens of persistent organic pollutants like PCBs, which potentially can interact and enhance the effects of other endocrine disruptors.