Perigestational exposure of a combination of a high-fat diet and pesticide impacts the metabolic and microbiotic status of dams and pups; a preventive strategy based on prebiotics.

PURPOSE: Metabolic changes during the perinatal period are known to promote obesity and type-2 diabetes in adulthood via perturbation of the microbiota. The risk factors for metabolic disorders include a high-fat diet (HFD) and exposure to pesticide residues. The objective of the present study was to evaluate the effects of perigestational exposure to a HFD and chlorpyrifos (CPF) on glycemia, lipid profiles, and microbial populations in Wistar dams and their female offspring. We also tested a preventive strategy based on treatment with the prebiotic inulin. METHODS: From 4 months before gestation to the end of the lactation period, six groups of dams were exposed to either a standard diet, a HFD alone, CPF alone, a combination of a HFD and CPF, and/or inulin supplementation. All female offspring were fed a standard diet from weaning to adulthood. We measured the impacts of these exposures on glycemia, the lipid profile, and the microbiota (composition, metabolite production, and translocation into tissues). RESULTS: HFD exposure and CPF + HFD co-exposure induced dysmetabolism and an imbalance in the gut flora in both the dams and the female offspring. Inulin mitigated the impact of exposure to a HFD alone but not that of CPF + HFD co-exposure. CONCLUSION: Our results provide a better understanding of the complex interactions between environmental pollutants and diet in early life, including in the context of metabolic diseases.

Chronic Perigestational Exposure to Chlorpyrifos Induces Perturbations in Gut Bacteria and Glucose and Lipid Markers in Female Rats and Their Offspring.

An increasing burden of evidence is pointing toward pesticides as risk factors for chronic disorders such as obesity and type 2 diabetes, leading to metabolic syndrome. Our objective was to assess the impact of chlorpyrifos (CPF) on metabolic and bacteriologic markers. Female rats were exposed before and during gestation and during lactation to CPF (1 mg/kg/day). Outcomes such as weight, glucose and lipid profiles, as well as disturbances in selected gut bacterial levels, were measured in both the dams (at the end of the lactation period) and in their female offspring at early adulthood (60 days of age). The results show that the weight of CPF dams were lower compared to the other groups, accompanied by an imbalance in blood glucose and lipid markers, and selected gut bacteria. Intra-uterine growth retardation, as well as metabolic disturbances and perturbation of selected gut bacteria, were also observed in their offspring, indicating both a direct effect on the dams and an indirect effect of CPF on the female offspring. Co-treatment with inulin (a prebiotic) prevented some of the outcomes of the pesticide. Further investigations could help better understand if those perturbations mimic or potentiate nutritional risk factors for metabolic syndrome through high fat diet.

Effect of Spermatic Nuclear Quality on Live Birth Rates in Intracytoplasmic Sperm Injection.

BACKGROUND: Our study defines the clinical role of sperm DNA damage in the assisted reproductive technology procedure. AIM: To investigate if the compaction of chromatin explored added to the analysis of the sperm DNA fragmentation allows obtaining a new indicator for sperm genome quality linked to live birth rate (LBR). DESIGN: This was a prospective study, undergoing 101 cycles in the intracytoplasmic sperm injection (ICSI) program. MATERIALS AND METHODS: The sperm DNA fragmentation index (DFI) has been measured with sperm chromatin dispersion examination. The sperm decondensation index (SDI) of chromatin has been measured with aniline blue procedure; with these indexes, a new parameter has been created: DFI × SDI. STATISTICAL ANALYSIS: Pearson's correlation coefficient, Student's t-test, and Chi-square test were used. The quantitative variables were described as mean ± standard deviation. Multivariate logistic regressions were performed with live birth as outcome. RESULTS: The sperm concentration, motility, and normal morphology were lower when the DFI was high (P = 0.001). The fertilization rates and the number of obtained embryos were not statistically significant different according to the DFI groups. The SDI does not appear to be linked either with the spermatic parameters or with the ICSI parameters. A low DFI seems to be a beneficial factor to obtain a live birth in ICSI procedure (P = 0.064). In case of high DFI, a high SDI allows to obtain a higher LBR than a low SDI. CONCLUSION: The DFI is a good prognostic for a delivery rate in ICSI procedure, and the SDI could be added to DFI to create a new parameter of sperm nuclear quality. This new parameter seems to be linked to LBR.

Metabolic syndrome, leptin-insulin resistance and uric acid: a trinomial foe for Algerian city-dweller adolescents' health.

Background Adolescence is one of the critical periods where increased risk for long-term obesity-related complications is an important health concern. This highlights the need to perform early diagnostics based on precise biomarkers to decrease the risk of complications in adolescents with obesity. Objective To determine the relationships between serum levels of uric acid (UA), leptin and insulin with metabolic syndrome (MS) components in Algerian adolescents. Subjects Nondiabetic adolescents (n = 204). Methods Blood pressure (BP) and anthropometric measurements were performed using standardized techniques. Blood samples were taken for determination of glycemia, triglyceridemia, uricemia, cholesterolemia, leptinemia and insulinemia. Results The rate of MS among an excess weight group was 17.4% [95% confidence interval (CI)]. Serum levels of UA, leptin and insulin were significantly higher in the excess weight group compared to a normal weight group (279.4 ± 86.05 vs. 204.9 ± 50.34 µmol/L and 25.65 ± 14.01 vs. 4.09 ± 2.60 µg/L, p < 0.001; 24.58 ± 13.85 vs. 13.34 ± 6.41 µIU/L, p < 0.05). Serum levels of UA, leptin and insulin were significantly higher in adolescents with MS compared to those without MS (304.86 ± 111.41 vs. 224.72 ± 77.81 µmol/L, 30.26 ± 12.46 vs. 16.93 ± 14.97 µg/L and 30.91 ± 17.30 vs. 18.71 ± 10.14 µIU/L, p < 0.05, respectively). Significant correlations were found between UA and leptin with waist circumference (r = 0.50 and 0.76), diastolic blood pressure (r = 0.58 and 0.43), triglycerides (r = 0.42 and 0.35) and high-density lipoprotein-cholesterol (r = -0.36 and -0.35). Conclusion Serum levels of UA and leptin may be useful biomarkers for early diagnosis of the risk of MS in our Algerian adolescent population.

Relationships between metabolic profile, hypertension and uric acid with cardiometabolic risk in adolescents with abdominal obesity: impact of geodemographic factors on the prevalence of abdominal obesity.

Background Association of hyperuricemia, dyslipidemia and high blood pressure (BP) among adolescents with high waist-to-height ratio (WHtR) remains not fully addressed and could represent a new way to diagnose adolescents early with cardiometabolic risk. Objective We aimed to determine abdominal obesity (AO) prevalence and investigate relations between AO, uric acid (UA), lipid profiles, BP and geographical patterns in adolescents. Subjects 577 and 204 Algerian students aged between 10 and 19 years were included in our epidemiological and biochemical studies, respectively. Methods Height, weight, waist circumference (Wc) and hip circumferences, body mass index (BMI) and BP were measured. Fasting blood sampling was performed to measure glycemia, lipid profile, uricemia, insulinemia and leptinemia. The WHtR ≥0.50 was applied for the diagnosis of AO and geodemographics was evaluated. Results The prevalence of AO was 12.13% among all students, 19.17% and 16.39% among students living in urban and plain areas, respectively. The risk of AO may be reduced in rural and mountainous areas. Lipid parameters, UA, insulin and leptin serum concentrations were significantly increased in adolescents with WHtR ≥0.50 compared to those with WHtR <0.50. Cardiometabolic risk was increased with WHtR ≥0.50 and BMI >26. Means of BMI, Wc, BP, and lipid parameters were significantly increased in the fourth quartiles compared to the first quartile of UA. Conclusion Urban areas and plains represent factors contributing to AO and WHtR ≥0.50 may be used as a cut-off point to define risks of high BP, lipid abnormalities and UA serum level in Algerian adolescents.

γ-sarcoglycan and dystrophin mutation spectrum in an Algerian cohort.

INTRODUCTION: We report the genetic analysis of a large series of 76 Algerian patients from 65 unrelated families who presented with early onset severe muscular dystrophy and a clinical phenotype resembling limb-girdle muscular dystrophy type 2C. METHODS: To define the genetic basis of the diseases in these families, we undertook a series of analyses of the γ-sarcoglycan (SGCG) and DMD genes. RESULTS: Fifteen families were shown to carry SGCG variants. Only 2 kinds of causative mutations were identified in the population, mostly in the homozygous state: the well-known c.525delT and the previously described c.87dupT. In the DMD gene, 12 distinctive patterns of deletion were identified, mostly affecting the dystrophin central region. CONCLUSIONS: Our data suggest that a simple molecular screen consisting of 2 allele-specific polymerase chain reactions (PCRs) and a set of 3 multiplex PCRs can diagnose half of the patients who present with progressive muscular dystrophy in the developing nation of Algeria. Muscle Nerve 56: 129-135, 2017.

Contribution of BRCA1 and BRCA2 Germline Mutations to Early Algerian Breast Cancer.

Breast cancer is the most common female malignancy and the leading cancer mortality cause among Algerian women. Germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast cancer have not been clearly identified within the Algerian population. It is necessary to study the BRCA1/2 genes involvement in the Algerian breast cancer occurrence. We performed this study to define germline mutations in BRCA1/2 and their implication in breast cancer among young women from eastern Algeria diagnosed or treated with primary invasive breast cancer at the age of 40 or less who were referred to Anti-Cancer Center of Setif, Algeria. Case series were unselected for family history. Eight distinct pathogenic mutations were identified in eight unrelated families. Three deleterious mutations and one large genomic rearrangement involving deletion of exon 2 were found in BRCA1 gene. In addition, four mutations within the BRCA2 gene and one large genomic rearrangement were identified. Novel mutation was found among Algerian population. Moreover, five variants of uncertain clinical significance and favor polymorphisms were identified. Our data suggest that BRCA1/2 mutations are responsible for a significant proportion of breast cancer in Algerian young women.

Oral Fat Sensing and CD36 Gene Polymorphism in Algerian Lean and Obese Teenagers.

Growing number of evidences have suggested that oral fat sensing, mediated by a glycoprotein CD36 (cluster of differentiation 36), plays a significant role in the development of obesity. Indeed, a decreased expression of CD36 in some obese subjects is associated with high dietary fat intake. In the present study, we examined whether an increase in body mass index (BMI) is associated with altered oleic acid lingual detection thresholds and blood lipid profile in young Algerian teenagers (n = 165). The obese teenagers (n = 83; 14.01 ± 0.19 years; BMI z-score 2.67 ± 0.29) exhibited higher lingual detection threshold for oleic acid than lean participants (n = 82, 13.92 ± 0.23 years; BMI z-score 0.03 ± 0.0001). We also studied the association between rs1761667 polymorphism of CD36 gene and obesity. The AA and AG genotypes were more frequent in obese teenagers, whereas GG genotype was more common in lean participants. The A-allele frequency was higher in obese teenagers than that in lean children. We report that rs1761667 polymorphism of CD36 gene and oro-gustatory thresholds for fat might play a significant role in the development of obesity in young teenagers.

Mutations of the aurora kinase C gene causing macrozoospermia are the most frequent genetic cause of male infertility in Algerian men.

Klinefelter syndrome and Y-chromosomal microdeletion analyses were once the only two genetic tests offered to infertile men. Analyses of aurora kinase C (AURKC) and DPY19L2 are now recommended for patients presenting macrozoospermia and globozoospermia, respectively, two rare forms of teratozoospermia particularly frequent among North African men. We carried out genetic analyses on Algerian patients, to evaluate the prevalence of these syndromes in this population and to compare it with the expected frequency of Klinefelter syndrome and Y-microdeletions. We carried out a retrospective study on 599 consecutive patients consulting for couple infertility at the assisted reproduction unit of the Ibn Rochd Clinique, Constantine, Algeria. Abnormal sperm parameters were observed in 404 men. Fourteen and seven men had typical macrozoospermia and globozoospermia profiles, respectively. Molecular diagnosis was carried out for these patients, for the AURKC and DPY19L2 genes. Eleven men with macrozoospermia had a homozygous AURKC mutation (79%), corresponding to 2.7% of all patients with abnormal spermograms. All the men with globozoospermia studied (n = 5), corresponding to 1.2% of all infertile men, presented a homozygous DPY19L2 deletion. By comparison, we would expect 1.6% of the patients in this cohort to have Klinefelter syndrome and 0.23% to have Y-microdeletion. Our findings thus indicate that AURKC mutations are more frequent than Klinefelter syndrome and constitute the leading genetic cause of infertility in North African men. Furthermore, we estimate that AURKC and DPY19L2 molecular defects are 10 and 5 times more frequent, respectively, than Y-microdeletions.