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1.
Int J Cancer ; 148(1): 99-105, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32930425

RESUMO

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.

2.
Int J Hyg Environ Health ; 231: 113635, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33091684

RESUMO

BACKGROUND: Maternal occupational exposure to organic solvents during pregnancy has been associated with decreased visual function in offspring. Glycol ethers (GEs) belong to oxygenated solvents and are widely used both in occupational and domestic contexts. OBJECTIVES: We aimed to assess associations between prenatal GEs exposure and contrast sensitivity in children. METHODS: Six GE alkoxy carboxylic acidic metabolites (methoxyacetic acid [MAA], ethoxyacetic acid [EAA], ethoxyethoxyacetic acid [EEAA], butoxyacetic acid [BAA], phenoxyacetic acid [PhAA], and 2-methoxypropionic acid [2-MPA]) were measured in first morning void urine samples collected from 220 early-pregnancy women, in the mother-child PELAGIE cohort (France). Trained investigators administered the Functional Acuity Contrast Test (FACT) to the 6-year-old children, providing scores for 5 spatial frequencies (1.5-18 cycles per degree (cpd)). We standardized biomarker urinary concentrations on urine sampling conditions. Values below the LOD were imputed based on log-normal distribution, generating five datasets for multiple imputation. Linear regression models were adjusted for potential confounders. RESULTS: GE metabolites were detected in 70-98% of maternal urine samples. Phenoxyacetic acid (PhAA) had the highest median concentration (0.33 mg/L), and 2-methoxypropionic acid (2-MPA) the lowest (0.01 mg/L). Children with higher prenatal PhAA concentrations had poorer FACT scores at various spatial frequencies (fourth vs. first quartile: ß18cpd = -0.90 (95% confidence interval CI = -1.64, -0.16), ß12cpd = -0.92 (95%CI = -1.55, -0.29) and ß1.5cpd = -0.69 (95%CI = -1.19, -0.20)). The 2-MPA log-scale concentration was negatively associated with the FACT score at the 3-cpd stimulus. DISCUSSION: PhAA is the metabolite of ethylene glycol monophenyl ether present in many cosmetics. 2-MPA is the metabolite of an isomer of propylene glycol methyl ether commonly present in household and industrial cleaning products. Although evidence of biological plausibility is lacking, the study suggests adverse impact of ubiquitous prenatal exposure to some GE on visual functioning among children.

3.
Eur Urol ; 78(3): 316-320, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32409115

RESUMO

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.

4.
Am J Trop Med Hyg ; 102(6): 1463-1465, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32285767

RESUMO

Desert dust transported from the Sahara to the Caribbean generates peak exposures to particulate matter ≤ 10 µm (PM10). We investigated the impact of dust episodes on severe small for gestational-age births in Guadeloupe. The study sample consisted of 911 pregnant women enrolled in the Timoun mother-child cohort. Desert dust exposure was assessed through the mean daily PM10 concentrations averaged over the entire pregnancy. Numerous sociodemographic and medical risk factors were considered as covariates and introduced into multinomial logistic regression models. Odds ratios (ORs) were calculated per SD change (3.08 µg/m3). Among various outcomes, symmetrically growth-retarded births showed the highest OR (3.28, 95% CI: 1.08-10.02). Saharan dust seems to influence weight but not length or head circumference at birth. Given the high OR observed in this study, it is conceivable that Saharan dust plays a role through severe placental insufficiency early in pregnancy.


Assuntos
Peso ao Nascer , Poeira , Monitoramento Ambiental , Retardo do Crescimento Fetal , Idade Gestacional , Exposição Materna , Adulto , África , Região do Caribe , Feminino , Humanos , Gravidez , Resultado da Gravidez
5.
Int J Hyg Environ Health ; 227: 113510, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32172156

RESUMO

Glycol ethers are an oxygenated solvent family widely present in consumer products. Some of them are recognized reproductive, developmental or hematological toxicants. Although several glycol ether biomonitoring studies have been performed on adults from working or general populations, no studies have hitherto been carried out on children. The aim of our study was to explore the detection of glycol ether metabolites in the urinary samples of 6-year-old children, and if any were found, to describe them. The PELAGIE mother-child cohort included 3421 pregnant women from the general population of Brittany, France, between 2002 and 2006. Our biomonitoring study included a random sample of 110 children from the PELAGIE cohort who had participated in a neurodevelopment evaluation at the age of six. First morning voids were collected from all of the children. Eight urinary glycol ether metabolites were measured using gas chromatography with mass spectrometry. The limit of detection was 0.003 mg/L for all metabolites. Glycol ether metabolites were detected at rates varying from 33.5% of samples for propoxyacetic acid to 100% of samples for phenoxyacetic acid and methoxyacetic acid. The highest median concentration observed was for phenoxyacetic acid (0.141 mg/l). Our study reported the ubiquitous presence of glycol ether metabolites in children's urinary samples. These results call for larger biomonitoring surveys of the general population and study of the potential sources and determinants of these exposures.

6.
Neurotoxicology ; 78: 195-201, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32217184

RESUMO

Recent evidence suggests that prenatal exposure to chlordecone, a persistent organochlorine pesticide that was used intensively in the French West Indies, affects infant neurodevelopment. The aim of the present study was to evaluate the association between prenatal and postnatal chlordecone exposures on visual contrast sensitivity in 285 children aged from 7.1 to 8 years old (mean age = 7.68 ±â€¯0.21 years; sex ratio = 54 % girls) in a Guadeloupean prospective birth cohort (TIMOUN). The Freiburg Visual Acuity and Contrast Test (FrAcT) was used to assess visual contrast sensitivity. Chlordecone concentrations were measured in blood samples at birth (cord blood) and in children at testing time to estimate pre- and postnatal exposure, respectively. Exposures were categorized into three groups and were also log-transformed and considered as continuous variables. Multiple linear regression models were performed on all children taking into account various potential confounders, including maternal characteristics (age, education, intellectual functioning, alcohol and tobacco use during pregnancy). Potential moderation effect of sex was also examined. Results showed that higher cord plasma chlordecone levels were associated with lower contrast sensitivity. Although child chlordecone levels was not associated with the FrAcT, sex-specific stratified analyses revealed significant associations in boys. Associations between postnatal exposure and FrACT scores in girls were null. This study indicates that exposure to chlordecone in utero and during childhood may impair visual contrast sensitivity at school age, particularly in boys.

7.
Environ Sci Pollut Res Int ; 27(33): 40992-40998, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31376129

RESUMO

Chlordecone is an organochlorine pesticide that was extensively used to control the banana root borer population in the French West Indies until 1993. Its persistence in soil has led to widespread pollution of the environment, and human beings, including pregnant women, are still exposed to this chemical. High levels of exposure to chlordecone during gestation have been shown to cause congenital anomalies, including undescended testes in rodents. We assessed the associations between chlordecone concentrations in maternal and cord plasma and the risk of congenital anomalies in the Timoun Mother-Child Cohort Study (2004-2007) that included 1068 pregnant women in Guadeloupe. Odds ratios were estimated using unconditional logistic regression analysis, controlling for confounding factors. The median plasma concentrations in maternal and cord plasma were 0.39 µg/L and 0.20 µg/L, respectively. Thirty-six children were diagnosed with malformations according to the European Registration of Congenital Anomalies guidelines and 25 with undescended testes. There was no association between maternal or cord plasma concentration of chlordecone and the risk of overall malformations nor undescended testes. These results suggest that prenatal exposure to the currently observed environmental levels of chlordecone in French West Indies does not increase the risk of birth defects.


Assuntos
Clordecona , Inseticidas , Criança , Clordecona/análise , Estudos de Coortes , Feminino , Guadalupe , Humanos , Inseticidas/análise , Mães , Gravidez , Índias Ocidentais
8.
Environ Sci Pollut Res Int ; 27(33): 41014-41022, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31621027

RESUMO

Chlordecone, an organochlorine insecticide, was widely used in the French West Indies banana plantations. We set up a cohort of banana plantation workers who worked between 1973 and 1993, the period of authorized use of chlordecone. Vital status and causes of death were collected from French national registries. Workers were followed up from 1 January 2000 to 31 December 2015. Cause-specific mortality in the cohort was compared to that of the general population of the French West Indies by computing standardized mortality ratios (SMRs). A total of 11,112 workers (149,526 person-years, 77% men) were included in the mortality analysis, and 3647 deaths occurred over the study period. There was a slight deficit in all-cause mortality, which was statistically significant in men (SMR = 0.93, 95% CI 0.89-0.96), but not in women (SMR = 0.96, 95% CI 0.89-1.04). All-cancer mortality did not differ significantly from that of the general population (men: SMR = 0.96, 95% CI 0.90-1.03; women: SMR = 1.04, 95% CI 0.89-1.21). Significant excesses of deaths were observed for stomach cancer in women (SMR = 1.94, 95% CI 1.24-2.89) and pancreatic cancer in women farm owners (SMR = 2.31, 95% CI 1.06-4.39). Mortality from prostate cancer was similar to that of the general population in the whole cohort (SMR = 1.00; 95% CI 0.89-1.13) and non-significantly elevated among farm workers (SMR = 1.10, 95% CI 0.87-1.36). Non-significant increases in mortality were also observed for lung cancer in women, leukemia in men, and non-Hodgkin lymphoma in both genders.


Assuntos
Musa , Neoplasias , Doenças Profissionais , Exposição Ocupacional , Estudos de Coortes , Feminino , Humanos , Masculino , Índias Ocidentais
9.
Environ Sci Pollut Res Int ; 27(33): 40971-40979, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31264154

RESUMO

Chlordecone was used intensively as an insecticide in the French West Indies. Because of its high persistence, the resulting contamination of food and water has led to chronic exposure of the general population as evidenced by its presence in the blood of people of Guadeloupe, in particular in pregnant women and newborns, and in maternal breast milk. Chlordecone is recognized as a reproductive and developmental toxicant, is neurotoxic and carcinogenic in rodents, and is considered as an endocrine-disrupting compound with well-established estrogenic and progestogenic properties both in vitro and in vivo. The question arises of its potential consequences on child neurodevelopment following prenatal and childhood exposure, in particular on behavioral sexual dimorphism in childhood. We followed 116 children from the TIMOUN mother-child cohort study in Guadeloupe, who were examined at age 7. These children were invited to participate in a 7-min structured play session in which they could choose between different toys considered as feminine, masculine, or neutral. The play session was video recorded, and the percentage of the time spent playing with feminine or masculine toys was calculated. We estimated associations between playtime and prenatal exposure to chlordecone (assessed by concentration in cord blood) or childhood exposure (determined from concentrations in child blood obtained at the 7-year follow-up), taking into account confounders and co-exposures to other environmental chemicals. We used a two-group regression model to take into account sex differences in play behavior. Our results do not indicate any modification in sex-typed toy preference among 7-year-old children in relation with either prenatal or childhood exposure to chlordecone.


Assuntos
Clordecona , Inseticidas , Criança , Clordecona/análise , Estudos de Coortes , Feminino , Guadalupe , Humanos , Recém-Nascido , Masculino , Leite Humano/química , Gravidez , Índias Ocidentais
10.
Int J Cancer ; 146(3): 657-663, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30892691

RESUMO

Previous studies have suggested that exposure to environmental chemicals with hormonal properties, also called endocrine disrupting chemicals, may be involved in the occurrence of prostate cancer (PCa). Such exposure may also influence the treatment outcome as it is still present at the time of diagnosis, the beginning of therapy, and beyond. We followed 326 men in Guadeloupe (French West Indies) who underwent radical prostatectomy as primary treatment of localized PCa. We analyzed the relationship between exposure to the estrogenic chlordecone, the antiandrogenic dichlorodiphenyldichloroethylene (DDE, the main metabolite of the insecticide DDT), and the nondioxin-like polychlorinated biphenyl congener 153 (PCB-153) with mixed estrogenic/antiestrogenic properties and the risk of biochemical recurrence (BCR) after surgery. After a median follow-up of 6.1 years after surgery, we found a significant increase in the risk of BCR, with increasing plasma chlordecone concentration (adjusted hazard ratio = 2.51; 95% confidence interval: 1.39-4.56 for the highest vs. lowest quartile of exposure; p trend = 0.002). We found no associations for DDE or PCB-135. These results shown that exposure to environmental estrogens may negatively influence the outcome of PCa treatment.


Assuntos
Disruptores Endócrinos/efeitos adversos , Poluentes Ambientais/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Prostatectomia , Neoplasias da Próstata/patologia , Idoso , Clordecona/efeitos adversos , Clordecona/sangue , Diclorodifenil Dicloroetileno/efeitos adversos , Diclorodifenil Dicloroetileno/sangue , Intervalo Livre de Doença , Poluentes Ambientais/sangue , Seguimentos , Guadalupe , Humanos , Inseticidas/efeitos adversos , Inseticidas/sangue , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/etiologia , Bifenilos Policlorados/efeitos adversos , Bifenilos Policlorados/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Fatores de Risco
11.
Andrologia ; 51(10): e13423, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31571259

RESUMO

The aim of our study was to evaluate the relationship between maternal tobacco consumption during pregnancy and sperm parameters and sexual hormonal levels of their sons in adulthood. We conducted a cross-sectional study in four medical institutions in Argentina, between June 1999 and June 2015, among male partners of couples consulting for infertility. At inclusion, a structured interview was conducted to obtain information on the basic demographic, medical, surgical and reproductive history, personal tobacco consumption and that of their parents during pregnancy. Two semen analyses at an interval of 2-4 weeks and a blood hormone evaluation (FSH, LH, prolactin, total testosterone and oestradiol) were then ordered. Analyses using multivariate models adjusted for potential confounders were performed for 537 men. Maternal tobacco consumption during pregnancy was associated with a significantly higher risk of reduced sperm count and elevated total testosterone levels. We did not find any significant association between maternal smoking and other sperm parameters nor other hormone levels. Our study adds evidence concerning the association between maternal tobacco consumption during pregnancy and reduced sperm counts of their sons in adulthood. The results showing an association between elevated total testosterone levels and maternal tobacco consumption need to be replicated.


Assuntos
Infertilidade Masculina/diagnóstico , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Análise do Sêmen/estatística & dados numéricos , Fumar/efeitos adversos , Adulto , Estudos Transversais , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/etiologia , Hormônio Luteinizante/sangue , Masculino , Exposição Materna/estatística & dados numéricos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Prolactina/sangue , Fumar/epidemiologia , Testosterona/sangue
12.
Front Pediatr ; 7: 269, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355164

RESUMO

Childhood obesity prevalence has increased over the last 30 years. The Heart Rate Variability (HRV) studies performed in adults suggest a possible relation between abnormal autonomic regulation and hypertension in the situation of overweight or obesity. Objective: The aims of this study were to explore the early relationships between adiposity and blood pressure and HRV in pre-pubertal children. Methods: Data were collected during the medical examination of the follow-up at 7 years of the TIMOUN mother-child cohort in Guadeloupe. Body Mass Index z-score (zBMI), sum of tricipital and subscapular skinfold thickness, percentage of fat mass, and Waist-to-Height Ratio were measured. A global corpulence score was computed using a Principal Component Analysis (PCA). Systolic Blood Pressure (SBP) and HRV parameters (cardiac holter monitoring) were collected under 2 conditions (calm and tachycardial period). Relations between HRV, SBP, each adiposity indicator and the corpulence score were studied with restricted cubic splines models, and linear regression models. The age at adiposity rebound (AR) was estimated from the individual growth curves. Results: 575 children were included in the SBP study (mean age: 7.7 years, from 85 to 99 months). SBP was linearly correlated with the corpulence score and the zBMI. An increase of 1 in the zBMI was associated with an increase of 2.3 (±0.28) mmHg in SBP. The effect-size of zBMI on SBP was higher in children with early age at AR. Compared to children with normal BMI, children with a zBMI <™2SD had their RMSSD, SDNN, LF and HF indicators in tachycardial conditions significantly reduced by -30, -21, -37, and -48%, respectively. In boys with a zBMI >2SD, we observed a global increase in all HRV parameters (under tachycardial conditions), particularly the LF [ß = 0.43 (±0.18)]. Conclusion: In pre-pubertal period a positive correlation between adiposity excess and SBP was observed with significant changes of HRV in boys, arguing for an early abnormal autonomic regulation and for early preventive intervention in the infancy period, particularly in case of overweight or obesity. Thinness was associated with a reduction in almost all the HRV parameters studied, when compared to normal corpulence, suggesting a decrease in autonomic influence.

13.
Epigenetics Chromatin ; 12(1): 29, 2019 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-31084621

RESUMO

Chlordecone (CD) is an insecticide that was used in the French West Indies for several years to control the banana root borer pest. Given its nonsignificant degradation, it persists in the environment. CD is a carcinogenic compound with reproductive and developmental toxicity and is a recognized endocrine-disrupting chemical. In this study, we examined the effects of CD on female reproductive system of mice with the focus on epigenetic features in ovary. Our data show that gestational exposure to low dose of CD affects meiotic double-strand breaks repair in female embryos. In adult mice derived from CD-treated pregnant females, we observed delayed puberty, decreased number of primordial and increased number of atretic follicles. Gene expression analysis revealed that Rcbtb2 and Rbpms genes were not expressed in embryonic gonads. Estrogen signaling- and oocyte maturation-associated genes were downregulated in adult ovaries. The morphological changes were associated with altered epigenetic features: increased H2Aub and increased H3K27me3 and decreased H4ac and H3K4me3 in embryonic oocytes. The DNA damage-associated, γH2AX marks were detected in the follicles of treated but not control adult ovaries. We also found reduced H3K4me3 and H4ac in fully grown oocytes of the treated ovaries. The ChIP-seq analysis of H3K4me3 in adult ovaries showed that target genes of ZFP57 and TRIM28, which regulate pluripotency and imprinting, were significantly enriched in altered regions. Our study clearly demonstrates that gestational exposure to a low dose of CD impairs the function of female reproductive system and the changes are associated with altered epigenetic features.


Assuntos
Clordecona/efeitos adversos , Epigênese Genética/efeitos dos fármacos , Ovário/efeitos dos fármacos , Animais , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Epigênese Genética/genética , Epigenômica/métodos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Genitália Feminina/efeitos dos fármacos , Inseticidas/efeitos adversos , Camundongos , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Oogênese/efeitos dos fármacos , Ovário/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal
14.
Occup Environ Med ; 76(5): 336-340, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30885977

RESUMO

OBJECTIVES: Large amounts of mineral dust are transported from their African sources in the Saharan-Sahel region to the Caribbean Sea, generating peak exposures to particulate matter ≤10 µm (PM10). This study aimed to investigate the impact of Saharan dust episodes on preterm births in the Guadeloupe archipelago. METHODS: The study population consisted of 909 pregnant women who were enrolled in the TIMOUN mother-child cohort between 2004 and 2007. Desert dust episodes were assessed from PM10 concentrations recorded at the unique background air quality monitoring station located in Pointe-à-Pitre. For each woman, the daily PM10 concentrations were averaged over the entire pregnancy, and the proportion of days with intense dust episodes (≥55 µg PM10/m3) during pregnancy was calculated. Weighted logistic regression models adjusting for known individual sociomedical risk factors were used to estimate ORs and 95% CIs for preterm birth. RESULTS: During pregnancy, the mean PM10 concentrations ranged from 13.17 to 34.92 µg/m3, whereas the proportion of intense dust events ranged from 0.00% to 19.41%. Increased adjusted ORs were found for both the mean PM10 concentrations and the proportion of intense dust events (OR 1.40, 95% CI 1.08 to 1.81, and OR 1.54, 95% CI 1.21 to 1.98 per SD change, respectively). Restriction to spontaneous preterm births produced similar ORs but with wider 95% CIs. CONCLUSION: Considering the personal and social burden of this adverse pregnancy outcome, this finding is of importance for both healthcare workers and policy makers to provide necessary preventive measures.


Assuntos
Minerais/efeitos adversos , Nascimento Prematuro/etiologia , Adulto , Poluentes Atmosféricos/análise , Região do Caribe/epidemiologia , Estudos de Coortes , Poeira/análise , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Minerais/metabolismo , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/metabolismo
15.
Trop Med Health ; 47: 4, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30651715

RESUMO

Background: A high rate of preterm birth is observed in the Guadeloupe archipelago (French West Indies), raising the hypothesis of harmful environmental exposures, including landfilling. Our aim was to evaluate whether preterm births cluster around the three main open landfills located in this area. Methods: The study population consisted of 911 women enrolled in the Timoun mother-child cohort (2004-2007). Home addresses during pregnancy and locations of landfills were geocoded. To test for the presence of preterm birth clusters around each dumpsite, we used a focused cluster test specifically designed to detect spatial clustering around point sources. Results: A total of 144 (15.8%) preterm births were observed among 911 births. Using the term births (n = 767) as controls, a significant cluster was identified within 2 km around the Saint-François landfill with a relative risk (RR) of 4.82 (p = 0.04). No clusters were found around the other two landfills (RR = 2.01, p = 0.26 and RR = 1.06, p = 0.64, for La Gabarre and Baillif, respectively). Conclusion: The paucity of data available on open landfill sites regarding waste quantities, composition, and changes over time precludes any site-specific interpretation because of the variable degree of possible emissions. This result has to be confirmed in other tropical island environments where waste management has become a major concern with the potential to negatively impact the environment and public health.

16.
Eur Urol ; 75(1): 11-15, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30245085

RESUMO

Causes of high mortality of prostate cancer in men of African ancestry living in the French West Indies are still debated, between suspicions of environmental factors and genetic susceptibility. We report an integrated genomic study of 25 tumour tissues from radical prostatectomy of aggressive (defined by International Society of Urological Pathology ≥3) prostate cancer patients (10 African Caribbean and 15 French Caucasian) using single nucleotide polymorphism arrays, whole-genome sequencing, and RNA sequencing. The results show that African Caribbean tumours are characterised by a more frequent deletion at 1q41-43 encompassing the DNA repair gene PARP1, and a higher proportion of intrachromosomal rearrangements including duplications associated with CDK12 truncating mutations. Transcriptome analyses show an overexpression of genes related to androgen receptor activity in African Caribbean tumours, and of PVT1, a long non-coding RNA located at 8q24 that confirms the strong involvement of this region in prostate tumours from men of African ancestry. Patient summary: Mortality of prostate cancer is higher in African Caribbean men than in French Caucasian men. Specificities of the former could be explained by genomic events linked with key genes such as DNA damage pathway genes PARP1, CDK12, and the oncogenic long non-coding RNA gene PVT1 at the 8q24 prostate cancer susceptibility locus.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Europeu/genética , Neoplasias da Próstata/genética , Região do Caribe/etnologia , Humanos , Masculino , Mutação , Polimorfismo de Nucleotídeo Único , Prostatectomia , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Sequenciamento Completo do Genoma
18.
Sci Rep ; 8(1): 10274, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980752

RESUMO

Environmental factors can affect epigenetic events during germline reprogramming and impose distinctive transgenerational consequences onto the offspring. In this study, we examined the transgenerational effects of chlordecone (CD), an organochlorine insecticide with well-known estrogenic properties. We exposed pregnant mice to CD from embryonic day 6.5 to 15.5 and observed a reduction in spermatogonia (SG) numbers in F3, meiotic defects in spermatocytes and decrease in spermatozoa number in the first and third generation of male progeny. The RNA qRT-PCR expression analysis in F1 and transcriptomics analysis in F3 males using the whole testes revealed changes in the expression of genes associated with chromosome segregation, cell division and DNA repair. The expression of the master regulator of pluripotency, Pou5f1, decreased in foetal and increased in adult F1, but not in F3 adult testes. Analysis of histone H3K4me3 distribution revealed widespread changes in its occupancy in the genome of F1 and F3 generations. We established that 7.1% of altered epigenetic marks were conserved between F1 and F3 generations. The overlapping changes common to F1 and F3 include genes implicated in cell adhesion and transcription factor activities functions. Differential peaks observed in F1 males are significantly enriched in predicted ESR1 binding sites, some of which we confirmed to be functional. Our data demonstrate that CD-mediated impairment of reproductive functions could be transmitted to subsequent generations.


Assuntos
Clordecona/toxicidade , Epigênese Genética , Regulação da Expressão Gênica/efeitos dos fármacos , Inseticidas/toxicidade , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Espermatogônias/patologia , Animais , Metilação de DNA , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Histonas/metabolismo , Masculino , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Contagem de Espermatozoides , Espermatogônias/efeitos dos fármacos
19.
Asian J Androl ; 20(4): 360-365, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29516876

RESUMO

Chronic epididymitis and varicocele are frequently observed genital disorders in men consulting for couple infertility, but their impact on semen characteristics at the time of infertility consultation is still a matter of debate. We investigated 652 male partners of couples who had their first infertility consultation between 1999 and 2015 in Argentina. Men with chronic epididymitis (n = 253), Grade III varicocele (n = 106), and both conditions (n = 125) were compared with a control group (n = 168) composed of men without these disorders or any other recognized causes of male infertility. We showed that men who presented isolated chronic epididymitis were more likely to have high percentages of low sperm motility and abnormal sperm morphology as well as a high number of white blood cells. Men with isolated Grade III varicocele had low sperm production and motility and an increased percentage of abnormal sperm morphology. Finally, men who simultaneously presented chronic epididymitis with Grade III varicocele had a low sperm motility and increased percentage of abnormal sperm morphology as well as a high number of white blood cells. Physical examination of the genital organs may identify common disorders, potentially involved as causal factors of patient's infertility. These disorders are associated with specific seminal profiles that should help in identifying the best treatment from the available therapeutic options, effectiveness, safety, and allowing as much as possible natural conception.


Assuntos
Epididimite/patologia , Infertilidade Masculina/patologia , Sêmen/citologia , Varicocele/patologia , Adulto , Argentina , Doença Crônica , Humanos , Masculino , Análise do Sêmen , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides/patologia
20.
Mol Cell Endocrinol ; 475: 74-91, 2018 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-29481862

RESUMO

Based on rodent studies after prenatal and/or perinatal or adult exposure, there is now evidence that BPA may increase metabolic disturbances eventually leading to type-2 diabetes development via an ED MoA. In particular, BPA has been shown to alter insulin synthesis and/or release by pancreatic ß-cells, and insulin signaling within insulin-sensitive organs (i.e., liver, muscle, adipose tissues). This resulted in variations in the expression of specific hepatic or adipose tissue markers, which are indicative of a state of insulin resistance. These effects are considered by experts to be hallmarks of adverse hormonal effects, each leading to insulin resistance within the different insulin-sensitive tissues. Although epidemiological studies are inconclusive, these effects are considered relevant for humans, because similarities exist in homeostatic regulation of insulin production and sensitivity between rodents and humans and because evidence was also shown through in vitro experimental data using human cells or tissues.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Metabolismo/efeitos dos fármacos , Fenóis/toxicidade , Animais , Humanos , Resistência à Insulina , Obesidade/metabolismo
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