Placental Toxicology of pesticides

GLADIS MAGNARELLI AND NATALIA GUIÑAZU

The Human Placenta",

InTech - Open Access Publisher

Año: 2012; p. 95 - 118

Considering that pathological conditions in the placenta are important causes of intrauterine, perinatal or maternal death, and a great deal of mother and child morbidity, understanding the impact of xenobiotics in the placenta is a major concern to toxicologists. In earlier times, the placenta was regarded as an organ protecting the fetus from exposures to toxic chemicals. We now understand that they may cross through the placenta and enter fetal blood stream. Placenta also interferes with xenobiotic delivery to the fetus, by expressing active membrane transporters and xenobiotic metabolism enzymes. The regulation of these enzymes and transporters and the effects of genetic polymorphisms on their function may have important implications in fetal and placental exposure to xenobiotics and their potential toxicities. In addition, some toxicants may accumulate in the placenta potentially affecting its development and or function. Therefore, understanding what the placenta does to xenobiotics and what they do to the placenta, should provide the basis for the use of this organ as a tool to investigate and predict some aspects of developmental toxicity. In this sense, placenta is a key tool for biomonitoring xenobiotic exposure. It is easy to collect and provides a large sample amount for analysis. Placenta is often the most accessible and readily available component of the triad mother-infant-placenta. It shows cumulative effects of pregnancy-related events, reflects the intrauterine environment, and may be examined to a degree that infant usually cannot. A critical issue for placenta toxicological analysis is the avaibility and appropriate use of biomarkers, which   provide measures of the exposure, toxic effects and individual susceptibility to toxicants. However, as epidemiological studies cannot control all the confounding factors, experimental designs are also needed. Thus, in vitro, in vivo and ex vivo models  have been used to elucidate toxicology of toxicants  in the human placenta. However, they have some limitations. Despite common physiological functions, the placentas of different species are heterogeneous in their morphology, transport and metabolism of xenobiotics,    raising the difficulty of obtaining a good representative model of human placenta. Moreover, changes in placental function due to chemical exposition may also depend on the gestational period in which exposition occurs. As consequence, information about   biochemical and  molecular toxicity of xenobiotics in human placenta is scarce because it is a difficult subject for research. This chapter will give an update about placenta toxicity of two families of pesticides: Organochhorine (OC) and organophosphate (OP). A link between exposure to these compounds during the gestational period and adverse reproductive outcomes, recurrent miscarriage, low birth weight, increased risk of malformations and intrauterine growth restriction were reported. OC are persistent and ubiquiotous environmental contaminants which have been restricted or banned in industrialized nations, and their contamination levels have disminished or are expected to decline. However, some of these chemicals are still used in developing countries. Due to their high lipophilicity and slow breakdown, they bioaccumulate  in the adipose tissue. During pregnancy, OC stored in maternal adipose tissue can be mobilized and enter her blood circulation and reach the placenta. Although there is not a clear and precise model for the bioaccumulation of OC in this organ, it is known that some OC metabolites selectively accumulate in the placenta suggesting a tissue specific metabolic activity. OC high lipophilicity favours their incorporation in biomembranes. Therefore, membrane bound enzymes, phospholipid metabolism and signalling pathways are sensible to OC deleterious effects as shown in Table I. Because of their widespread and intensive use, OP are considered as a pesticide class of great interest for the study of environmental health. Conversely to OC, they are rapidly metabolized and excreted, therefore, OP metabolites are usually determined in fluids as maternal urine or cord blood. Although the placenta is a non innervated organ, the presence of cholinergic system has been demonstrated by unequivocal methods. Acetilcholinesterase, the primary target of OP derived oxon metabolite as well as carboxilesterases, the secondary one, may be used as exposition biomarkers. Regarding the possible mechanisms intervening in the pathogenesis of placenta injury by OP, a broad spectrum of non cholinergic targets appears in scene such as: impaired mitochondrial bioenergetics, hormonal and immune disruption. Both types of pesticides, OC and OP, have demonstrated to mediate some of their toxic events by oxidative stress, which is likely a major contributing factor to trophoblast injury and placenta disfunction. According to the above considerations, this chapter would provide a comprehensive discussion on the molecular and biochemical bases of pesticides effects on the human placenta, and on the usefullness of biomarkers in placenta for toxicological analysis. Future challenges as placenta  micro array, epigenetic studies and effects of pesticide mixtures would be briefly described.