Genome-wide temporal landscaping of DNA methylation in pregnant women delivering at term: a GARBH-InI study.

Background: We performed an epigenome-wide longitudinal DNA methylation study on an Indian cohort of pregnant women, GARBH-Ini, at three time points during pregnancy and at delivery. Aim & objective: Our aim was to identify temporal DNA methylation changes in maternal peripheral blood during the period of gestation and assess their impact on biological pathways critical for term delivery. Results: Significantly differentially methylated CpGs were identified by linear mixed model analysis (Bonferroni p < 0.01) and classified into two distinct temporal methylation trends: increasing and decreasing during gestation. Genes with upward methylation trend were enriched for T-cell activity, while those with a downward trend were enriched for solute transport and cell structure organization functions. Conclusion: Consistent trends of DNA methylation in maternal peripheral blood point to the sentinel function of T cells in the maintenance of pregnancy, and the importance of coordinated cellular remodeling to facilitate term delivery.

DNA methylation is the addition of a methyl group to the molecular structure of DNA, which then alters the gene expression. The goal of the study was to find out how DNA methylation patterns change over time during pregnancy and how these changes are related to the biological processes that are important for the delivery of a healthy baby at full term. Using statistical modeling, we identified specific patterns of DNA methylation changes during pregnancy and classified them into two groups based on the direction of the changes. The genes associated with increasing methylation levels were related to the activities of T cells, which are important for the immune system. The genes associated with decreasing methylation levels were related to processes like transporting substances and organizing cell structures. In conclusion, our findings suggest that T cells play an important role in maintaining a healthy pregnancy, and the study highlights the importance of coordinated changes in cells to support a successful delivery of a baby at term.

Investigating spatial distribution of fluoride in groundwater with respect to hydro-geochemical characteristics and associated probabilistic health risk in Baruipur block of West Bengal, India.

Fluoride (F-) enrichment in groundwater of the lower Gangetic plain in West Bengal, India is a major concern. Fluoride contamination and its toxicity were reported earlier in this region; however, limited evidence was available on the precise site of contamination, hydro-geochemical attributions of F- mobilization and probabilistic health risk caused by fluoridated groundwater. The present study addresses the research gap by exploring the spatial distribution and physico-chemical parameters of fluoridated groundwater along with the depth-wise sedimental distribution of F-. Approximately, 10 % of the groundwater samples (n = 824) exhibited high F- ≥ 1.5 mg/l from 5, out of 19 gram-panchayats and Baruipur municipality area and the maximum F- was observed in Dhapdhapi-II gram-panchayat with 43.7 % of samples showed ≥1.5 mg/l (n = 167). The distribution patterns of cations and anions in fluoridated groundwater were Na+ > Ca2+ > Mg2+ > Fe > K+ and Cl- > HCO3- > SO42- > CO32- > NO3- > F-. Different statistical models like Piper and Gibbs diagram, Chloro Alkaline plot, Saturation index were applied to better understand the hydro-geochemical characteristics for F- leaching in groundwater. Fluoridated groundwater is of Na-Cl type which implies strong saline character. The intermediate zone between evaporation and rock dominance area controls F- mobilization along with ion-exchange process occurring between groundwater and host silicate mineral. Furthermore, saturation index proves geogenic activities related to groundwater F- mobilization. All cations present in sediment samples are closely interlinked with F- in the depth range of 0-18.3 m. Mineralogical analyses revealed that muscovite is the most responsible mineral for F- mobilization. The probabilistic health risk assessment disclosed severe health hazard in the order of infants > adults > children > teenagers through F- tainted groundwater. At P95 percentile dose, all the studied age groups showed THQ >1 from Dhapdhapi-II gram-panchayat. Supply of F- safe drinking water is required through reliable water supply strategies in the studied area.

Different levels of arsenic exposure through cooked rice and its associated benefit-risk assessment from rural and urban populations of West Bengal, India: a probabilistic approach with sensitivity analysis.

Rice arsenic (As) contamination and its consumption poses a significant health threat to humans. The present study focuses on the contribution of arsenic, micronutrients, and associated benefit-risk assessment through cooked rice from rural (exposed and control) and urban (apparently control) populations. The mean decreased percentages of As from uncooked to cooked rice for exposed (Gaighata), apparently control (Kolkata), and control (Pingla) areas are 73.8, 78.5, and 61.3%, respectively. The margin of exposure through cooked rice (MoEcooked rice) < 1 signifies the existence of health risk for all the studied exposed and control age groups. The respective contributions of iAs (inorganic arsenic) in uncooked and cooked rice are nearly 96.6, 94.7, and 100% and 92.2, 90.2, and 94.2% from exposed, apparently control, and control areas. LCR analysis for the exposed, apparently control, and control populations (adult male: 2.1 × 10-3, 2.8 × 10-4, 4.7 × 10-4; adult female: 1.9 × 10-3, 2.1 × 10-4, 4.4 × 10-4; and children: 5.8 × 10-4, 4.9 × 10-5, 1.1 × 10-4) through cooked rice is higher than the recommended value, i.e., 1 × 10-6, respectively, whereas HQ > 1 has been observed for all age groups from the exposed area and adult male group from the control area. Adults and children from rural area showed that ingestion rate (IR) and concentration are the respective influencing factors towards cooked rice As, whereas IR is solely responsible for all age groups from urban area. A vital suggestion is to reduce the IR of cooked rice for control population to avoid the As-induced health risks. The average intake (µg/day) of micronutrients is in the order of Zn > Se for all the studied populations and Se intake is lower for the exposed population (53.9) compared to the apparently control (140) and control (208) populations. Benefit-risk assessment supported that the Se-rich values in cooked rice are effective in avoiding the toxic effect and potential risk from the associated metal (As).

Significance of the prime factors regulating arsenic toxicity and associated health risk: a hypothesis-based investigation in a critically exposed population of West Bengal, India.

The suffering from arsenic toxicity is a long-standing concern in Asian countries. The role of the key factors (arsenic intake, age and sex) regulating arsenic toxicity is aimed to evaluate for a severely exposed population from Murshidabad district, West Bengal. Mean arsenic concentrations in drinking water supplied through tube well, Sajaldhara treatment plant and pipeline were observed as 208, 27 and 54 µg/l, respectively. Urinary arsenic concentration had been observed as < 3-42.1, < 3-56.2 and < 3-80 µg/l in children, teenagers and adults, respectively. Mean concentrations of hair and nail arsenic were found to be 0.84 and 2.38 mg/kg; 3.07 and 6.18 mg/kg; and 4.41 and 9.07 mg/kg, respectively, for the studied age-groups. Water arsenic was found to be associated with hair and nail (r = 0.57 and 0.60), higher than urine (r = 0.37). Arsenic deposition in biomarkers appeared to be dependent on age; however, it is independent of sex. Principal component analysis showed a direct relationship between dietary intake of arsenic and chronic biomarkers. Nail was proved as the most fitted biomarker of arsenic toxicity by Dunn's post hoc test. Monte Carlo sensitivity analysis and cluster analysis showed that the most significant factor regulating health risk is 'concentration of arsenic' than 'exposure duration', 'body weight' and 'intake rate'. The contribution of arsenic concentration towards calculated health risk was highest in teenagers (45.5-61.2%), followed by adults (47.8-49%) and children (21-27.6%). Regular and sufficient access to arsenic-safe drinking water is an immediate need for the affected population.

Emergence of a unique SARS-CoV-2 Delta sub-cluster harboring a constellation of co-appearing non-Spike mutations.

Accumulation of diverse mutations across the structural and nonstructural genes is leading to rapid evolution of SARS-CoV-2, altering its pathogenicity. We performed whole genome sequencing of 239 SARS-CoV-2 RNA samples collected from both adult and pediatric patients across eastern India (West Bengal), during the second pandemic wave in India (April-May 2021). In addition to several common spike mutations within the Delta variant, a unique constellation of eight co-appearing non-Spike mutations was identified, which revealed a high degree of positive mutual correlation. Our results also demonstrated the dynamics of SARS-CoV-2 variants among unvaccinated pediatric patients. 41.4% of our studied Delta strains harbored this signature set of eight co-appearing non-Spike mutations and phylogenetically out-clustered other Delta sub-lineages like 21J, 21A, or 21I. This is the first report from eastern India that portrayed a landscape of co-appearing mutations in the non-Spike proteins, which might have led to the evolution of a distinct Delta subcluster. Accumulation of such mutations in SARS-CoV-2 may lead to the emergence of "vaccine-evading variants." Hence, monitoring of such non-Spike mutations will be significant in the formulation of any future vaccines against those SARS-CoV-2 variants that might evade the current vaccine-induced immunity, among both the pediatric and adult populations.

Maternal DNA Methylation During Pregnancy: a Review.

Multiple environmental, behavioral, and hereditary factors affect pregnancy. Recent studies suggest that epigenetic modifications, such as DNA methylation (DNAm), affect both maternal and fetal health during the period of gestation. Some of the pregnancy-related risk factors can influence maternal DNAm, thus predisposing both the mother and the neonate to clinical adversities with long-lasting consequences. DNAm alterations in the promoter and enhancer regions modulate gene expression changes which play vital physiological role. In this review, we have discussed the recent advances in our understanding of maternal DNA methylation changes during pregnancy and its associated complications such as gestational diabetes and anemia, adverse pregnancy outcomes like preterm birth, and preeclampsia. We have also highlighted some major gaps and limitations in the area which if addressed might improve our understanding of pregnancy and its associated adverse clinical conditions, ultimately leading to healthy pregnancies and reduction of public health burden.