Polyhalogenated aromatic arylhydrocarbons (PAHs) such as polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), the polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent lipophilic pollutants, which affect female fertility resulting in severe reproductive dysregulation, including anovulation, reduced conception rates, abortion, menstrual abnormalities and developmental defects of female reproductive tissues. Many PAHs exert their effects by activating a family of basic helix-loop-helix (bHLH) transcription factors, the arylhydrocarbon receptor (AhR) and the arylhydrocarbon receptor nuclear translocator (ARNT), which result in the expression of AhR target molecules. Complex interactions between PAH-mediated AhR activation and ER signalling pathways have been discovered which may contribute to the developmental malformations, impact on reproductive dysfunctions and promote carcinogenic dedifferentiation of tissues within the female reproductive tract. This review will focus on the multifaceted roles of PAHs in key organs of the female reproductive tract, the ovary, uterus/ endometrium and the mammary gland. The complexity and diversity of actions unleashed by PAHs in these female reproductive tissues identify these environmental pollutants as important endocrine disrupting toxicants impacting on female fertility.
Dept. of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, 130 Basic Medical Sciences Bldg. Winnipeg, Manitoba, R3E 0W3, Canada.
Publication date: March 1, 2005
More about this publication?
Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.