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The proximity to areas of intensive pesticide application is a risk factor that favors xenobiotic exposure. Pesticides may interfere with hormonal function and cause alterations in the reproductive system, pregnancy complications, and adverse fetal development. We evaluated potential endocrine disruption and the evolution of the third trimester of pregnancy in women residing in a rural area of Argentina with intense pesticide applications, and the characteristics of their newborns. Blood samples were collected from healthy women in the third trimester of pregnancy during the pesticide spraying (SP) (n = 26) and nonspraying (NSP) (n = 27) periods. Plasma cholinesterase activity and cortisol and DHEA-S levels were lower in SP than in NSP. The percentage of preterm premature rupture of membranes was higher in SP than in NSP. Macrosomia at birth was17% in both periods. This study reinforces the importance of preventing potential cases of cumulative toxicity during the perinatal period through monitoring and epidemiological studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In rural populations, the proximity to areas with intensive pesticide application represents a risk factor of xenobiotic exposure. Here, we investigated whether newborns born to mothers residing in an area with intensive pesticide application show alterations in placental and neonatal morphometric standards, umbilical cord blood (UCB) biochemical parameters, and/or biomarkers related to oxidative stress and oxidative damage. Samples were collected from 151 healthy pregnant women residing in a rural area (rural group; RG) during the pesticide spraying (SS) and nonspraying (NSS) seasons, as well as from women from an urban population (control group; CG), and grouped according to the delivery type (vaginal or cesarean). In the vaginal delivery group, the placental weight and placental index were higher in the RG groups than in the CG (p = 0.01), whereas in the cesarean delivery group, newborn weight was lower in the RG-SS group than in the CG. In the RG-SS group, UCB erythrocyte osmotic fragility and the DNA damage index (DI) were higher, and superoxide dismutase (SOD) activity was lower than in the RG-NSS group. Acetylcholinesterase and SOD activities were found to be inversely correlated with the DI.

The impact of environmental organophosphate (OP) pesticide exposure on respiratory complexes, enzymatic antioxidant defense activities, and oxidative damage markers in the syncytiotrophoblast and cytotrophoblast mitochondria was evaluated. Placental progesterone (PG) levels and endothelial nitric oxide synthase (eNOS) expression were studied. Samples from women non-exposed (control group-CG) and women living in a rural area (rural group-RG) were collected during pesticide spraying season (RG-SS) and non-spraying season (RG-NSS). In RG-SS, the exposure biomarker placental carboxylesterase decreased and syncytiotrophoblast cytochrome c oxidase activity increased, while 4-hydroxynonenal levels decreased. PG levels decreased in RG-SS and in the RG. Nitric oxide synthase expression decreased in RG, RG-SS and RG-NSS. No significant changes in mitochondrial antioxidant enzyme activities were found. These results suggest that the alteration of syncytiotrophoblast mitochondrial complex IV activity and steroidogenic function may be associated to pesticide exposure. Reduction in placental PG and eNOS expression may account for low newborn weight in RG., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The impact of environmental organophosphate pesticide exposure on the placenta oxidative status was assessed. Placental samples were collected from women residing in an agricultural area during pesticide pulverization period, non-pulverization period and from control group. Carboxylesterase activity was significantly decreased in pulverization period group. Enzymatic and non-enzymatic defense system, the oxidative stress biomarkers and the nuclear factor erythroid 2-related factor levels showed no differences among groups. However, in the pulverization period group, an inverse association between catalase activity and placental index, a useful metric for estimating placental inefficiency, was found. This result suggests that catalase may serve as a potential placental biomarker of susceptibility to pesticides. Further studies designed from a gene-environment perspective are needed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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, TGFβ 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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Blood cholinesterases and tissue carboxylesterases (CEs) are sensitive indicators of environmental organophosphate pesticides (OPs) exposure. The aim of this pilot study was to assess the impact of OP exposure on placental CE activity and lipid composition. We performed a study of 40 healthy women who live in agricultural farms. Samples were collected during the pulverization period (PP) and recess period (RP). The plasma cholinesterase and placental CE activity decreased in PP, suggesting that women were exposed to OPs and that these pesticides reached the placenta. The cardiolipin content increased and the phosphatidylethanolamine content decreased in the light mitochondrial fraction while total cholesterol and sphingomyelin increased in the nuclear fraction. These changes in lipid profiles suggest repair by hyperplasia of the cytotrophoblast. Decreased CE activity may have clinical and toxicological implications and thus entail potential risks to damage fetal growth and development., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In utero exposure is the first point of contact with environmental xenobiotics that may affect the maternal-placental-fetal balance. Considering that maternal pathophysiological changes affect intrauterine development, this pilot study was conducted to address how environmental exposure to organophosphate pesticides (OPs) during pregnancy may contribute to maternal endocrine disruption and disturbed hepatic function. A prospective study was carried out with pregnant women (n=97) living in a rural area of the Rio Negro province where OPs are intensively applied throughout 6 months of the year. Blood samples were obtained and biomarkers of OPs exposure (cholinesterases and β-glucuronidase), cortisol (CT) and progesterone (PG) levels, as well as glycemia, were determined. Parameters of liver injury were assayed by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT); liver function was assayed by measuring albumin. Biomonitoring carried out during the pre-spraying period (PreS) and spraying period (SP) showed that the population studied was exposed to OPs, proven by the fact that plasma (PCh) and erythrocyte cholinesterase (AChE) decreased very significantly (p<0.01) during SP. CT values increased very significantly (p<0.01) in the first trimester of pregnancy during SP with respect to PreS. Individual values above the upper limit of the CT and PG reference range were found both in PreS and SP. This finding could be associated with changes in hormone metabolism pathways produced by OPs exposure. During the second trimester of pregnancy there were increases in ALT values and the AST/ALT ratio in SP, suggesting subclinical hepatotoxicity. In SP, glycemia was unchanged while albuminemia increased. Although anthropometric newborn parameters and pregnancy alterations were within normal values for the general population, the increase in CT in the maternal compartment may lead to impaired newborn health later in life., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

Pre- and perinatal exposure to pesticides is deleterious on foetal and neonatal development, but information regarding possible effects on environmental low-dose exposure to pesticides is scarce. Most epidemiological studies of the health effect of pesticides have been based on self-reported information. However, detailed information on past pesticide use is difficult to reconstruct. This is a current study conducted among pregnant mothers attending a delivery care and perinatal programme at a public hospital. The study investigates biomarkers of early effects in placentas from women living in an area with an intensive use of pesticides in the northern part of Patagonia, province of Río Negro, Argentina, and it assesses the consistency of the information provided by self-reports. The study confirms that placental acetylcholinesterase and catalase activities are significantly associated with periods of organophosphorus pesticides application, while glutathione S-transferase is not affected. We found a positive correlation between environmental exposure to organophosphorus pesticides and carbamate insecticides and newborn head circumference. The findings provide a further indication of a link between placenta acetylcholinesterase and catalase activity and prenatal exposure to pesticides in population studies. Both placenta enzymes may be used as biomarkers in health surveillance programmes for early diagnosis of exposure related alterations produced by organophosphorus pesticides and carbamate pesticides.