Persistent organic pollutants and bone tissue : Studies in wild and experimental animals

Detta är en avhandling från Stockholm : Karolinska Institutet, Institute of Enviromental Medicine

Sammanfattning: Since the mid 1900s, there has been a dramatic increase in the number of osteoporotic-related fractures in the industrialised world. The reason for this is unknown, but there could be a link between the increased use and production of chemicals and effects on bone. Many chemicals possess endocrine-disrupting properties, affecting reproductive tissues and other endocrine-regulated tissues, such as bone tissue. In this thesis, studies have been performed on wild (alligator and herring gull) as well as experimental animals (goat and rat) with the aim to investigate potential bone effects of different persistent organic pollutants (POPs), such as dicofol, DDT and its metabolites, polychlorinated biphenyls (PCBs) and dioxins. The methods used include peripheral quantitative computed tomography (pQCT), biomechanics (three-point bending test), mineralisation analysis (bone chemical composition), and measurements of the bone markers alkaline phosphatase (ALP) (bone formation) and carboxyterminal telopeptide of type I collagen (CTX) (bone resorption). The results in this thesis show that free-ranging female alligators residing in a pesticide-polluted lake (dicofol, DDT and its metabolites) in Florida, USA show increases in trabecular bone mineral density (BMD), total BMD and bone mineral content, compared to females from a control lake. The bone effects indicate exposure to an estrogenic environment, suggesting the mainly anti-androgenic p,p -DDE and/or the mainly estrogenic dicofol to elicit estrogenic actions on bone tissue homeostasis. Bone effects have been observed in free-ranging herring gulls residing in the Great Lakes, a lake system in North America polluted with POPs and metals and situated near many large cities and industries. Alterations include decreases in bone length, periosteal circumference, total cross-sectional area (CSA) and an increase in displacement at failure, compared to herring gulls from a freshwater reference site. The pQCT results indicate disrupted estrogen-signalling in bone tissue and in addition, the biomechanical results suggest disruption of the mineralisation process. This thesis also presents bone effects observed in experimental animals. Female goat offspring exposed to an environmentally relevant dose of the non dioxin-like putative estrogen PCB 153 in utero and through mother s milk had bone changes indicating estrogenic bone effects, such as increased trabecular BMD in the metaphysis and decreases of the total CSA, moment of resistance and marrow cavity in the diaphysis. However, the dioxin-like anti-estrogenic PCB 126 did not produce any developmental effects on goat bone. Interestingly, male rats exposed to a single high dose (LD50) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCCD) for only five days (short-term exposure) showed anti-estrogenic bone effects, such as decreased trabecular area, an increase of CTX, a decrease of ALP, and an altered bone chemical composition, resembling more mature bones. In conclusion, bone tissue is a likely target for endocrine-disrupting chemicals, hence, bone effects were observed in a various number of species exposed to POPs. The observed effects suggest POPs to exert anti-estrogenic or estrogenic actions on bone composition, dimensions and strength, or to disrupt the mineralisation process. However, further studies are needed in order to elucidate by what mechanisms pesticides, PCBs and dioxins exert their potential effect on bone tissue.

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