Pesticide Exposure Alters Follicle-Stimulating Hormone Levels in Mexican Agricultural Workers

Organophosphorous pesticides (OPs) are suspected of altering reproductive function by reducing brain acetylcholinesterase activity and monoamine levels, thus impairing hypothalamic and/or pituitary endocrine functions and gonadal processes. Our objective was to evaluate in a longitudinal study the association between OP exposure and serum levels of pituitary and sex hormones. Urinary OP metabolite levels were measured by gas–liquid chromatography, and serum pituitary and sex hormone levels by enzymatic immunoassay and radioimmunoassay in 64 men. A total of 147 urine and blood samples were analyzed for each parameter. More than 80% of the participants had at least one OP metabolite in their urine samples. The most frequent metabolite found was diethylthiophosphate (DETP; 55%), followed by diethylphosphate (DEP; 46%), dimethylthiophosphate (DMTP; 32%), and dimethyldithiophosphate (DMDTP; 31%). However, the metabolites detected at higher concentrations were DMTP, DEP, DMDTP, and dimethylphosphate. There was a high proportion of individuals with follicle-stimulating hormone (FSH) concentrations outside the range of normality (48%). The average FSH serum levels were higher during the heavy pesticide spraying season. However, a multivariate analysis of data collected in all periods showed that serum FSH levels were negatively associated with urinary concentrations of both DMTP and DMDTP, whereas luteinizing hormone (LH) was negatively associated with DMTP. We observed no significant associations between estradiol or testosterone serum levels with OP metabolites. The hormonal disruption in agricultural workers presented here, together with results from experimental animal studies, suggests that OP exposure disrupts the hypothalamic–pituitary endocrine function and also indicates that FSH and LH are the hormones most affected

Relationship between target organ damage and blood pressure, retinal vessel calibre, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes in patients with hypertension: a case-control study protocol (LOD- Hipertensión)

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license.[Introduction]: Target organ damage (TOD) is associated with increased cardiovascular risk. The study objectives were to analyse the relationship of TOD to blood pressure, size of retinal arteries and veins, oxidative stress and different polymorphisms in the VAV-2 and VAV-3 genes in participants with hypertension. [Methods and analysis]: A case-control study to analyse the relationship between clinical, biochemical and genetic parameters and presence of cardiac, vascular and renal TOD in 486 patients with hypertension. Participants with TOD will be considered as cases, and those without TOD will be enrolled as controls. This will be a collaborative study conducted by the groups of Primary Care, Cardiovascular and Metabolic and Degenerative Diseases of the Instituto de Investigación Biomédica of Salamanca (IBSAL). Assessment of cardiac, renal and vascular TOD. Measurement of peripheral and central blood pressure, size of eye fundus arteries and veins, and oxidative stress, and polymorphisms in the VAV-2 and VAV-3 genes. [Ethics and dissemination]: The study will be conducted after approval is obtained from the Ethics Committee of Hospital Clínico Universitario of Salamanca. All study participants will sign an informed consent to agree to participate in the study, and another consent to agree on the genetic study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow for an understanding of the relationship of the different TODs with blood pressure, retinal artery and vein diameters, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes. [Trial registration number]: Clinical Trials. gov Identifier: NCT02022618.This project has been supported by the Castilla y León Health Service (BIO/SA05/13), Carlos III Institute of Health of the Spanish Ministry of Health (RETICS RD12/0005, RedIAPP, and RD12/0021, RedinRen), and Infosalud Foundation.Peer Reviewe

Assessment of YAP gene polymorphisms and arsenic interaction in Mexican women with breast cancer

The identification of gene-environment interactions related to breast cancer reveals the biological and molecular mechanisms underlying the disease and allows the distinction of women at high risk from women at lower risk, which could decrease the morbimortality of this neoplasm. The current study evaluated the association between polymorphisms rs1820453 and rs11225161 of the Yes-associated protein (YAP) gene in women with breast cancer exposed to arsenic (As) through drinking water. In total, 182 women were assessed for the frequency of YAP rs1820453 and rs11225161 polymorphisms and As urinary levels. The results demonstrated a positive and significant association between breast cancer and smoking, type of drinking water, and levels of AsIII , AsV and inorganic As (iAs) but not the YAP gene polymorphisms evaluated. In conclusion, our data showed that the source of drinking water and AsV and iAs urinary levels increased the risk for breast cancer, but no interactions between YAP gene polymorphisms and As urinary levels were found.University of Coahuila; Superfund National Institute of Environmental Health Sciences [NIH ES-04940, NIEHS/NIH P30ES006694, P42ES004940];[CONACyT-377059]12 month embargo; published online: 21 October 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Association between the polymorphism of three genes involved in the methylation and efflux of arsenic (As3MT, MRP1, and P‐gp) with lung cancer in a Mexican cohort

Lung cancer is the most common neoplasm and the primary cause-related mortality in developed and in most of nondeveloped countries. Epidemiological studies have demonstrated that even at low arsenic doses, the lungs are one of the main target organs and that chronic arsenic exposure has been associated with an increase in lung cancer development. Among the risk factors for cancer, arsenic methylation efficiency (As3MT) and the clearance of arsenic from cells by two members of the ATP-binding cassette (ABC) transporter family (multidrug resistance protein 1 [MRP1] and P-glycoprotein [P-gp]) play an important role in processing of arsenic and decreasing its intracellular levels. This study aimed to evaluate the association between chronic exposure to arsenic with polymorphism of three proteins involved in arsenic metabolism and efflux of the metalloid in subjects with lung cancer. Polymorphism in As3MT, MRP1, and P-gp modified the arsenic metabolism increasing significantly the AsV urinary levels. A significant association between MRP1 polymorphisms with an increase in the risk for cancer was found. The high inorganic arsenic urinary levels registered in the studied subjects suggest a reduction in the efficiency of As3MT, MRP1, and P-gp firstly because of gene polymorphisms and secondarily because of high internal inorganic arsenic levels. MRP1 polymorphism was associated with a twofold increase in the risk of lung cancer. © 2020 John Wiley & Sons, Ltd.12 month embargo; first published: 19 December 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer

Objective. To assess whether in Mexican population the frequencies of ATM polymorphisms IVS24-9delT, IVS38-8T mayor que C, and 5557G mayor que A in breast cancer (BC) cases and healthy controls were different from those found in other countries. Materials and methods. Frequencies of polymorphisms conferring BC risk IVS24-9delT, IVS38-8T mayor que C, and 5557G mayor que A were analyzed by PCR-RFLP in 94 patients with familial and/or early onset BC, and 97 healthy controls randomly selected. Allele frequencies analysis was done using χ2 and Hardy-Weinberg test. Results. Frequencies of heterozygous were: for 5557G mayor que A, 13% cases, 0%controls (p=0.0009); for IVS24-9delT, 21% cases, 8% controls (p=0.0122); for IVS38-8T mayor que C, only one case. 5557G mayor que A and IVS24-9delT were more frequent in cases than in controls. The allelic frequencies found in 5557G mayor que A are similar to those described by González-Hormazábal in Chile. Conclusion. The similarity of results in this polymorphism between Chilean and Mexican populations may be due to both being crossbred with an Amerindian-Spanish component, while differences may be due to fact that Chilean population has a greater European component than Mexican’s

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Organophosphorous pesticides (OPs) are suspected of altering reproductive function by reducing brain acetylcholinesterase activity and monoamine levels, thus impairing hypothalamic and/or pituitary endocrine functions and gonadal processes. Our objective was to evaluate in a longitudinal study the association between OP exposure and serum levels of pituitary and sex hormones. Urinary OP metabolite levels were measured by gas-liquid chromatography, and serum pituitary and sex hormone levels by enzymatic immunoassay and radioimmunoassay in 64 men. A total of 147 urine and blood samples were analyzed for each parameter. More than 80% of the participants had at least one OP metabolite in their urine samples. The most frequent metabolite found was diethylthiophosphate (DETP; 55%), followed by diethylphosphate (DEP; 46%), dimethylthiophosphate (DMTP; 32%), and dimethyldithiophosphate (DMDTP; 31%). However, the metabolites detected at higher concentrations were DMTP, DEP, DMDTP, and dimethylphosphate. There was a high proportion of individuals with follicle-stimulating hormone (FSH) concentrations outside the range of normality (48%). The average FSH serum levels were higher during the heavy pesticide spraying season. However, a multivariate analysis of data collected in all periods showed that serum FSH levels were negatively associated with urinary concentrations of both DMTP and DMDTP, whereas luteinizing hormone (LH) was negatively associated with DMTP. We observed no significant associations between estradiol or testosterone serum levels with OP metabolites. The hormonal disruption in agricultural workers presented here, together with results from experimental animal studies, suggests that OP exposure disrupts the hypothalamicpituitary endocrine function and also indicates that FSH and LH are the hormones most affected

Association between YAP expression in neoplastic and non-neoplastic breast tissue with arsenic urinary levels

The Hippo pathway regulates cell proliferation and apoptosis and it has been noted that loss of critical components of this pathway can lead to uncontrolled cell growth. Yes-associated protein (YAP) is an important component of this Hippo pathway because YAP is the nuclear effector of the Hippo tumor suppressor pathway and it is crucial for the response to oxidative stress induced by cellular process and by different xenobiotics, including arsenic. It has been proposed that YAP dysregulation can contribute to a malignant cellular phenotype acting as both a tumor suppressor and an oncogene. The aim of the study was to assess and compare the expression of YAP in neoplastic and non-neoplastic breast tissue of women chronically exposed to arsenic through drinking water. YAP expression was assessed by immunohistochemistry in 120 breast biopsies from women with breast cancer and from women with other non-neoplastic breast pathologies. Arsenic concentration was quantified in urine. The results disclosed a significant lower percentage of cytoplasm YAP expression in cases and that YAP high-intensity staining in the cytoplasm but not in the nucleus decreases the risk for breast cancer. In conclusion, our overall data suggest that YAP may act as a tumor suppressor protein because their reduced expression in cases, which can induce an environment favorable for inhibition of apoptosis and promoting cellular proliferation by increasing genetic instability of cells, which might contribute to the pathogenesis of cancer.University of Coahuila; Superfund National Institute of Environmental Health Sciences [NIH ES-04940]12 month embargo; first published: 19 May 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Association between different risk factors and vascular accelerated ageing (EVA study): study protocol for a cross-sectional, descriptive observational study

[Introduction]: The process of population ageing that is occurring in developed societies represents a major challenge for the health system. The aim of this study is to analyse factors that have an influence on early vascular ageing (EVA), estimated by carotid-femoral pulse wave velocity (cf-PWV) and Cardio Ankle Vascular Index (CAVI), and to determine differences by gender in a Spanish population. [Methods and analysis]: An observational, descriptive, cross-sectional study. [Study population]: From the population assigned to the participating healthcare centres, a cluster random sampling stratified by age and gender will be performed to obtain 500 participants aged between 35 and 75. Those who meet the inclusion criteria and give written informed consent will be included in the study. [Measurements]: Main dependent variables: cf-PWV determined using the SphygmoCor System and CAVI estimated using VASERA. Secondary dependent variables: telomere length, carotid intima-media thickness, central and peripheral augmentation index, ankle-brachial pulse wave velocity, ankle-brachial index, retinal arteriovenous index, and renal and cardiac organ damage. Independent variables: lifestyles (physical activity, adherence to the Mediterranean diet, alcohol and tobacco consumption); psychological factors (depression, anxiety and chronic stress); inflammatory factors and oxidative stress. [Ethics and dissemination]: The study has been approved by the clinical research ethics committee of the healthcare area of Salamanca. All study participants will sign an informed consent form agreeing to participate in the study in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow the understanding of the relationship of the different influencing factors and their relative weight in the development of EVA. At least 5 publications in firstquartile scientific journals are planned. [Trial registration number]: NCT02623894; Pre-results.The project has been funded by the IBSAL; the Institute of Health Carlos III of the Ministry of Economy and Competitiveness (Spain) through the Network for Prevention and Health Promotion in Primary Care (redIAPP, RD12/0005), co-financed with European Union Health Institute/European Regional Development Fund (ERDF), the Autonomous Government of Castilla and León (GRS 1193/B/15) and intensification of research programme.Peer Reviewe