Environmental pesticide exposure modulates cytokines, arginase and ornithine decarboxylase expression in human placenta.

To evaluate the cytokine balance and enzymatic alterations induced by environmental pesticide exposure during pregnancy, this transversal study explored placentas derived from non-exposed women (control group-CG), and from women living in a rural area (rural group-RG), collected during intensive organophosphate (OP) pesticide spraying season (RG-SS) and during non-spraying season (RG-NSS). The exposure biomarkers blood cholinesterase and placental carboxylesterase (CaE) were significantly decreased in RG-SS. Among the cytokines studied IL-8, IL-6, TNFα, IL-10, TGFß and IL-13, the expression frequency of IL-13 increased in RG-SS. Arginase and ornithine decarboxylase (ODC) enzymes were induced in syncytiotrophoblast and endothelial cells. Interestingly, the decrease in CaE activity was associated with arginase and ODC activity induction. These findings suggest that environmental pesticide exposure impacts the placenta by increasing the expression frequency of the anti-inflammatory cytokine IL-13, which may be related to the up-regulation of enzymes implicated in tissue repair.

Organophosphate pesticide environmental exposure: analysis of salivary cholinesterase and carboxilesterase activities in preschool children and their mothers.

A pilot study was conducted to evaluate the usefulness of salivary cholinesterase and carboxylesterase as biomarkers of exposure to environmental organophosphate pesticides. Ninety samples were obtained from women and 62 samples from their preschool-aged children who live near an agricultural area of the Upper Valley of the Negro River (Patagonia, Argentina) where pesticides are applied 6 months a year. Each participant donated two samples under similar conditions: one in the pre-exposure period and another during the pulverization period. Demographic information, potential confounders, and risk behaviors were registered. Active or passive smoking had no effect on these enzyme activities in either group. During the pulverization period, cholinesterase activity was not detectable in 76% of the children's samples and 23% of the mothers' samples. Comparing samples collected during the pulverization period with respect to the pre-pulverization period, the average mother and child cholinesterase activity decreased by 65.7% (p < 0.001) and 85.8% (p < 0.001), respectively. Also, mother and child carboxylesterase activity decreased by 27.5% (p < 0.001) and 41.9% (p < 0.01), respectively. Child carboxylesterase activity in the pulverization period was associated to the habit of eating dust outdoors (p < 0.01). The most frequent inhibition levels observed for cholinesterase and carboxylesterase activity were between 70-100% and 0-29%, respectively, in both groups studied. This shows that at the same level of exposure, cholinesterase was more sensitive to inhibition than carboxylesterase. Therefore, carboxylesterase might more properly reflect the degree of environmental organophosphate exposure and may have potential as a novel tool for biomonitoring.

Exposición ambiental a plaguicidas: impacto en parámetros moleculares, bioquímicos y morfométricos de la tríada madre-placenta-feto / Environmental exposure to pesticides: impact on molecular, biochemical and morphometric parameters of the mother-placenta-fetus triad

INTRODUCCION:La salud prenatal representa un problema relevante de salud públic, y uno de los temas prioritarios es la exposición ambiental a los plaguicidas.OBJETIVO:Identificar modificaciones en biomarcadores de efecto en la tríada madre-placenta-feto, mecanismos involucrados y asociaciones con el desarrollo "in utero".METODOS:Se realizó un estudio prospectivo con 776 embarazadas del Alto Valle del Río Negro, donde se aplican organofosforados (OF) intensivamente. Se utilizaron criterios de inclusión/exclusión, determinándose parámetros bioquímicos, moleculares y morfométricos en población de comunidades rurales (PoR) en período de pulverizaciones (PP) y de receso (PR) y en grupo control (PoC). Se registraron las alteraciones del embarazo.RESULTADOS:En PP, la Por presentó exposición a OF, y se vieron afectados los niveles de progesterona, cortisol y sulfato de dehidroepiandrosterona séricos durante el embarazo. En sangre de cordón aumentó la actividad de catalasa eritrocitaria. En la placenta se modificaron biomarcadores de estrés oxidativo, de funcionalidad mitocondrial, la expresión de TNFò e IL-13 y el contenido de la proteína Bcl-2. En concordancia, en células JEG-3 expuestas a OF se observó estrés oxidativo, apoptosis y aumento en la expresión de dichas citoquinas. La talla y el perímetro cefálico ajustados por sexo y edad gestacional del neonato fueron menores en PoR que en PoC (p<0,010 y p<0,05, respectivamente), mientras que el porcentaje de neonatos con perímetro cefálico menor al percentilo 5 fue mayor. En PoR se registró un mayor porcentaje de amenaza de aborto. Los niveles maternos de cortisol de primer y segundo trimestre de embarazo de PoR se asociaron negativamente con el peso y el perímetro cefálico.CONCLUSIONES:En PoR se afectaron parámetros de la tríada y del desarrollo intrauterino. El aumento en el nivel de cortisol materno sobreexpondría al feto a esta hormona, afectando la programación del eje hipotalámico-adrenal y la capacidad cognitiva.

INTRODUCTION: Prenatal health represents a relevant problem in public health. Special attention should be given to pesticide environmental exposure.OBJECTIVE: To identify changes in biomarkers of effect in the triad mother-placenta-fetus, mechanisms involved and their association with the in utero development.METHODS: Prospective study of 776 pregnante woman living in the High Valley of Río Negro, where organophosphate pesticides (OP) are intensively applied. The study used inclusion/exclusion criteria. Biochemical, molecular and morphometric parameters were determined in rural residents (RR) in pulverization (PP) and recess periods (RP) and in a control group (CG). Pregnancy alterations were registered.RESULTS: In PP, RR were exposed to OP, while serum progesterone, cortisol and dehydroepiandrosterone sulfate levels were affected during pregnancy. In cord blood, erythrocyte catalase activity was increased. In the placenta, there was a change in stress oxidative biomarkers, mitochondrial function biomarkers, the expression of TNFò and IL-13 and the protein Bcl-2 content. In line with the above, JEG-3 cells exposed to OP showed oxidative stress, apoptosis and increase in these cytokines expression. In RR, the newborn length and heah circumference adjusted by sex and gestational age were lower (p<0.010 and p<0.05, respectively) than in CG. Meanwhile, the percentage of newborns with head circumference lower than percentile 5 was higher. In RR, a higher percentage of threatened abortion was registered. Cortisol blood levels at first and second trimester of pregnancy were negatively associated with newborn weight and head circumference.CONCLUSIONS: Parameters of the triad and intrauterine development were affected in RR. The increase in the level of maternal cortisol would overexpose the fetus to this hormone, affecting the programming of hypothalamic-adrenal axis and the cognitive ability.

Exposición ambiental a plaguicidas: impacto en parámetros moleculares, bioquímicos y morfométricos de la tríada madre-placenta-feto / Environmental exposure to pesticides: impact on molecular, biochemical and morphometric parameters of the mother-placenta-fetus triad

INTRODUCCION:La salud prenatal representa un problema relevante de salud públic, y uno de los temas prioritarios es la exposición ambiental a los plaguicidas.OBJETIVO:Identificar modificaciones en biomarcadores de efecto en la tríada madre-placenta-feto, mecanismos involucrados y asociaciones con el desarrollo "in utero".METODOS:Se realizó un estudio prospectivo con 776 embarazadas del Alto Valle del Río Negro, donde se aplican organofosforados (OF) intensivamente. Se utilizaron criterios de inclusión/exclusión, determinándose parámetros bioquímicos, moleculares y morfométricos en población de comunidades rurales (PoR) en período de pulverizaciones (PP) y de receso (PR) y en grupo control (PoC). Se registraron las alteraciones del embarazo.RESULTADOS:En PP, la Por presentó exposición a OF, y se vieron afectados los niveles de progesterona, cortisol y sulfato de dehidroepiandrosterona séricos durante el embarazo. En sangre de cordón aumentó la actividad de catalasa eritrocitaria. En la placenta se modificaron biomarcadores de estrés oxidativo, de funcionalidad mitocondrial, la expresión de TNFò e IL-13 y el contenido de la proteína Bcl-2. En concordancia, en células JEG-3 expuestas a OF se observó estrés oxidativo, apoptosis y aumento en la expresión de dichas citoquinas. La talla y el perímetro cefálico ajustados por sexo y edad gestacional del neonato fueron menores en PoR que en PoC (p<0,010 y p<0,05, respectivamente), mientras que el porcentaje de neonatos con perímetro cefálico menor al percentilo 5 fue mayor. En PoR se registró un mayor porcentaje de amenaza de aborto. Los niveles maternos de cortisol de primer y segundo trimestre de embarazo de PoR se asociaron negativamente con el peso y el perímetro cefálico.CONCLUSIONES:En PoR se afectaron parámetros de la tríada y del desarrollo intrauterino. El aumento en el nivel de cortisol materno sobreexpondría al feto a esta hormona, afectando la programación del eje hipotalámico-adrenal y la capacidad cognitiva.

INTRODUCTION: Prenatal health represents a relevant problem in public health. Special attention should be given to pesticide environmental exposure.OBJECTIVE: To identify changes in biomarkers of effect in the triad mother-placenta-fetus, mechanisms involved and their association with the in utero development.METHODS: Prospective study of 776 pregnante woman living in the High Valley of Río Negro, where organophosphate pesticides (OP) are intensively applied. The study used inclusion/exclusion criteria. Biochemical, molecular and morphometric parameters were determined in rural residents (RR) in pulverization (PP) and recess periods (RP) and in a control group (CG). Pregnancy alterations were registered.RESULTS: In PP, RR were exposed to OP, while serum progesterone, cortisol and dehydroepiandrosterone sulfate levels were affected during pregnancy. In cord blood, erythrocyte catalase activity was increased. In the placenta, there was a change in stress oxidative biomarkers, mitochondrial function biomarkers, the expression of TNFò and IL-13 and the protein Bcl-2 content. In line with the above, JEG-3 cells exposed to OP showed oxidative stress, apoptosis and increase in these cytokines expression. In RR, the newborn length and heah circumference adjusted by sex and gestational age were lower (p<0.010 and p<0.05, respectively) than in CG. Meanwhile, the percentage of newborns with head circumference lower than percentile 5 was higher. In RR, a higher percentage of threatened abortion was registered. Cortisol blood levels at first and second trimester of pregnancy were negatively associated with newborn weight and head circumference.CONCLUSIONS: Parameters of the triad and intrauterine development were affected in RR. The increase in the level of maternal cortisol would overexpose the fetus to this hormone, affecting the programming of hypothalamic-adrenal axis and the cognitive ability.