Toxicology and pathology of female reproductive tract

Abstract

The female reproductive tract is not commonly targeted in routine toxicity studies except with certain hormonal agents. Specific reproductive safety studies, on the other hand provide many positive findings. More recently, several environmental chemicals have shown to have impact on the reproductive functions often leading to infertility. The reproductive system is under constant influences by hormonal controls through the hypothalamus/pituitary/gonad axis (HPG axis). Chemical agents or factors producing effects on any of these loci can affect the reproductive tract. The morphology and function of female reproductive tract change markedly due to ageing, starting from infancy. These include stages such as infancy, puberty, adulthood and senility. There are interspecies differences in the onset of puberty, sexual maturity and senility, and awareness of these is essential, when toxicity studies are carried out in different laboratory animal species. Normally, the female reproductive tract of mature adults constantly manifests changes in morphology and function due to oestrous or menstrual cycles. Many of the agents produce changes in the reproductive tract that are similar to those found at different stages of the reproductive cycles. A clear understanding of the changes occurring at different stages of oestrous or menstrual cycles of the different laboratory animal species is essential for the correct interpretation of the study results. There are marked differences in these changes between the laboratory animal species and women. Some of the findings in animal studies do not have a counterpart in humans making safety extrapolation of some of the findings of less relevant. The female reproductive cycle is also strongly influenced by psychological influences. Endorphins and other local mediators play roles in gonadotropic release mechanisms in hypothalamus. Stress and extreme physical activity among female athletes, are known to suspend reproductive cycles due to their inhibitory effects on gonadotropic release. Thus, toxicity studies can also sometimes reveal nonspecific responses due to exposure to high doses, affecting the reproductive cycle.