👤 Marta Nazzari

Pregnancy constitutes a critical window of vulnerability during which maternal and environmental exposures may shape fetal development through epigenetic mechanisms. While prenatal maternal anxiety and exposure to green spaces have been independently associated with child neurodevelopment, their potential interactive effects on neonatal epigenetic profiles remain largely unexplored. This study examined the independent and interactive effects of maternal trait anxiety and residential green space exposure during pregnancy on neonatal DNA methylation (DNAm) of the brain-derived neurotrophic factor (BDNF) gene. A sample of 110 mother-infant dyads was enrolled at delivery. Maternal trait anxiety was assessed using the Stait-Trait Anxiety Inventory (STAI-Y) and infants' BDNF DNAm at birth was assessed in 11 CpG sites in buccal cells. Prenatal residential addresses were geocoded and green space availability within 300, 500, and 1000 m buffers was calculated using the CLCplus Backbone 2021 land cover dataset. Hierarchical linear regression models were adjusted for infant sex and prenatal exposure to PM2.5. Results indicated that higher maternal trait anxiety was associated with increased BDNF DNAm at four CpG sites only among infants with lower exposure to green space within a 300 m buffer. This association was not significant at higher levels of greenness, suggesting a neuroprotective effect of natural environments during gestation. Findings provide novel evidence that urban green space may buffer the biological impact of maternal anxiety on neonatal BDNF methylation. This highlights the importance of integrating psychological and environmental-level exposures to elucidate early-life determinants of neurodevelopment. Show less

Endocrine disruptors are compounds of manmade origin able to interfere with the endocrine system and constitute an important environmental concern. Indeed, detrimental effects on thyroid physiology and functioning have been described. Differences exist in the susceptibility of human sexes to the incidence of thyroid disorders, like autoimmune diseases or cancer. To study how different hormonal environments impact the thyroid response to endocrine disruptors, we exposed human embryonic stem cell-derived thyroid organoids to physiological concentrations of sex hormones resembling the serum levels of human females post-ovulation or males of reproductive age for three days. Afterwards, we added 10 µM benzo[a]pyrene or PCB153 for 24 h and analyzed the transcriptome changes via single-cell RNA sequencing with differential gene expression and gene ontology analysis. The sex hormones receptors genes AR, ESR1, ESR2 and PGR were expressed at low levels. Among the thyroid markers, only TG resulted downregulated by benzo[a]pyrene or benzo[a]pyrene with the "male" hormones mix. Both hormone mixtures and benzo[a]pyrene alone upregulated ribosomal genes and genes involved in oxidative phosphorylation, while their combination decreased the expression compared to benzo[a]pyrene alone. The "male" mix and benzo[a]pyrene, alone or in combination, upregulated genes involved in lipid transport and metabolism (APOA1, APOC3, APOA4, FABP1, FABP2, FABP6). The combination of "male" hormones and benzo[a]pyrene induced also genes involved in inflammation and NFkB targets. Benzo[a]pyrene upregulated CYP1A1, CYP1B1 and NQO1 irrespective of the hormonal context. The induction was stronger in the "female" mix. Benzo[a]pyrene alone upregulated genes involved in cell cycle regulation, response to reactive oxygen species and apoptosis. PCB153 had a modest effect in presence of "male" hormones, while we did not observe any changes with the "female" mix. This work shows how single cell transcriptomics can be applied to selectively study the in vitro effects of endocrine disrupters and their interaction with different hormonal contexts. Show less