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Background: Two different mitochondrial fractions (MFs) have been characterized in the human placenta: the "light" and "heavy" fractions (LMF and HMF). Although these organelles are the main source of reactive oxygen species, an imbalance between their production and the rate of detoxification represents a serious threat to mitochondrial homeostasis and, in the case of the placenta, also to the fetus. The aim of this study was to evaluate the antioxidant capacity and susceptibility to oxidative stress in both types of MFs., Methods: Human MFs were isolated from healthy donors (n = 11) and either incubated or not with H 2 O 2 . Catalase (CAT) activity, and reduced glutathione (GSH), lipid peroxidation (LP), and protein carbonylation (PC) levels were determined., Results: H 2 O 2 treatment increased LP and PC levels and decreased CAT activity. GSH levels were similar in control and treated MFs., Conclusion: H 2 O 2 caused oxidative damage in both LMF and HMF and the antioxidant system measured in these two MFs responded similarly. To the best of our knowledge, this is the first partial description of the antioxidant defense in placental HMF and LMF performed in a cell-free assay. The small number of antioxidant system parameters measured did not allow detecting differences between HMF and LMF., (© 2018 Wiley Periodicals, Inc.)

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.)

Organochlorine pesticides have been detected in placenta. The ability of heptachlor (HC) and 1,1,1-tricholoro-2-(2-chlorophenyl)-2-4-chlorophenyl)ethane (o-p'DDT) to interfere with protein phosphorylation was evaluated. In vitro incubations of cell-free placental villi homogenates with a concentration range 1-100 microM were performed. In particulate fractions, total serine/threonine kinase activity was increased by 10 microM HC and o-p' DDT (59% and 82%, respectively). Maximum eightfold increase was observed with 10 microM o-p' DDT on protein kinase A activity. By contrast, protein kinase C activity was reduced by 10 microM HC and o-p' DDT (40% and 52%, respectively). Endogenous substrate phosphorylation studies demonstrated that slight but significant increase in 24-kDa band labeling was produced in nuclear samples with 1, 10, and 100 microM HC and 100 microM o-p' DDT. Exposition to 100 microM HC increased 85-kDa band labeling. In mitochondrial fractions, 10 microM HC and o-p' DDT increased 24- and 65-kDa bands' labeling. These data indicate that both pesticides affect protein kinase activities in particulate fraction. Nuclear compartmentalization of these compounds, insertion in membranes, and chemical stress production may be associated to the observed effects, thus suggesting deleterious consequences in signaling pathways.

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.