Rossella Alfano's research while affiliated with Imperial College London and other places

Publications (28)

Article
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Background Rapid postnatal growth may result from exposure in utero or early life to adverse conditions and has been associated with diseases later in life and, in particular, with childhood obesity. DNA methylation, interfacing early-life exposures and subsequent diseases, is a possible mechanism underlying early-life programming. Methods Here, a...
Article
Background DNA methylation programming is sensitive to prenatal life environmental influences, but the impact of maternal exposure to green space on newborns DNA methylation has not been studied yet. Methods We conducted a meta-epigenome-wide association study (EWAS) of maternal exposure to green space during gestation with cord blood DNA methylat...
Article
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Telomere length at birth determines later life telomere length and potentially predicts ageing-related diseases. However, the genetic and epigenetic settings of telomere length in newborns have not been analyzed. In addition, no study yet has reported how the interplay between genetic variants and genome-wide cytosine methylation explains the varia...
Article
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Background Mitochondria play an important role in the energy metabolism and are susceptible to environmental pollution. Prenatal air pollution exposure has been linked with childhood obesity. Placental mtDNA mutations have been associated with prenatal particulate matter exposure and MT-ND4L10550A>G heteroplasmy has been associated with BMI in adul...
Article
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Background The mechanisms underlying childhood overweight and obesity are poorly known. Here, we investigated the direct and indirect effects of different prenatal exposures on offspring rapid postnatal growth and overweight in childhood, mediated through cord blood metabolites. Additionally, rapid postnatal growth was considered a potential mediat...
Article
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A growing number of children born are conceived through in vitro fertilisation (IVF), which has been linked to an increased risk of adverse perinatal outcomes, as well as altered growth profiles and cardiometabolic differences in the resultant individuals. Some of these outcomes have also been shown to be influenced by the use of different IVF cult...
Article
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Aging starts at the beginning of life as evidenced by high variability in telomere length (TL) and mitochondrial DNA content (mtDNAc) at birth. Whether p53 and PGC-1α are connected to these age-related markers in early life is unclear. In this study, we hypothesized that these hallmarks of aging are associated at birth. In 613 newborns from the ENV...
Article
Objective: Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring, a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized that changes in offspring DNA methylation (DNAm) underline these associations. Research design and methods: To address this hypothesis, we...
Article
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Childhood obesity has become a global epidemic and carries significant long-term consequences to physical and mental health. Metabolomics, the global profiling of small molecules or metabolites, may reveal the mechanisms of development of childhood obesity and clarify links between obesity and metabolic disease. A systematic review of metabolomic s...
Article
The tremendous increase in childhood obesity prevalence over the last few decades cannot merely be explained by genetics and evolutionary changes in the genome, implying that gene–environment interactions, such as epigenetic modifications, likely play a major role. This systematic review aims to summarize the evidence of the association between epi...
Article
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Introduction Metabolomics may identify biological pathways predisposing children to the risk of overweight and obesity. In this study, we have investigated the cord blood metabolic signatures of rapid growth in infancy and overweight in early childhood in four European birth cohorts. Methods Untargeted liquid chromatography-mass spectrometry metab...
Article
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Telomere length (TL) and telomere shortening are biological indicators of aging, and epigenetic associates have been found for TL in adults. However, the role of epigenetic signatures in setting newborn TL and early life telomere dynamics is unknown. In the present study, based on 247 participating newborns from the ENVIRONAGE birth cohort, whole-g...
Article
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Background Accumulating evidence links paternal adiposity in the periconceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans. Methods In the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of coord...
Article
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Background The IGF2 (insulin-like growth factor 2) and H19 gene cluster plays an important role during pregnancy as it promotes both foetal and placental growth. We investigated the association between cord blood DNA methylation status of the IGF2/H19 gene cluster and maternal fine particulate matter exposure during fetal life. To the best of our k...
Article
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Background Birthweight reflects in utero exposures and later health evolution. Despite existing studies employing high-dimensional molecular measurements, the understanding of underlying mechanisms of birthweight remains limited. Methods To investigate the systems biology of birthweight, we cross-sectionally integrated the methylome, the transcrip...
Preprint
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Background: Accumulating evidence links paternal adiposity in the peri-conceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans. Methods and findings: In the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-an...
Article
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According to the "Developmental Origins of Health and Disease" (DOHaD) concept, the early-life environment is a critical period for fetal programming. Given the epidemiological evidence that air pollution exposure during pregnancy adversely affects newborn outcomes such as birth weight and preterm birth, there is a need to pay attention to underlyi...
Article
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Mitochondrial dysfunction seems to play a key role in the etiology of insulin resistance. At birth, a link has already been established between mitochondrial DNA (mtDNA) content and insulin levels in cord blood. In this study, we explore shared epigenetic mechanisms of the association between mtDNA content and insulin levels, supporting the develop...
Article
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Background Socioeconomic experiences are recognized determinants of health, and recent work has shown that social disadvantages in early life may induce sustained biological changes at molecular level that are detectable later in life. However, the dynamics and persistence of biological embedding of socioeconomic position (SEP) remains vastly unexp...
Article
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Purpose of Review This systematic review evaluated existing evidence linking air pollution exposure in humans to major epigenetic mechanisms: DNA methylation, microRNAs, long noncoding RNAs, and chromatin regulation. Recent Findings Eighty-two manuscripts were eligible, most of which were observational (85%), conducted in adults (66%) and based on...
Article
Introduction Birthweight is a known risk factor for diseases in adult life however; the biomolecular mechanisms leading to disease processes remain poorly understood. DNA modifications, transcripts, proteins and metabolites have the potential to imprint biological responses during early life and drive adult risk profiles to chronic conditions. The...
Article
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Maternal exposure to airborne particulate matter (PM) has been associated with restricted foetal growth and reduced birthweight. Here, we performed methylome-wide analyses of cord and children's blood DNA in relation to residential exposure to PM smaller than 10µm (PM10). This study included participants of the Avon Longitudinal Study of Pregnancy...

Citations

... PGT has been employed as an embryo selection tool for patients undergoing in vitro fertilization (IVF) to ensure higher implantation rates or at least shorter gestational times [2]. PGT is an organic combination of assisted reproductive technology and modern molecular genetic diagnosis technology, and is an important part of preventive medicine [3]. Compared with prenatal diagnosis, the superiority of PGT lies in the screening and diagnosis of preimplantation embryos and the realization of eugenics from the source of pregnancy [1]. ...
... For instance, THMs have been demonstrated to induce DNA strand breaks in primary human lung epithelial cells (Landi et al., 2003), as well as DNA damage and impaired DNA repair capacity in human lymphoblastic leukemia cells (Geter et al., 2004). Meanwhile, telomere damage can cause mitochondrial compromise (Sahin et al., 2011), and mitochondrial dysfunction, in turn, can lead to changes in telomere biology (Lin and Epel, 2022;Van Der Stukken et al., 2022). Nevertheless, while sperm mitochondria and TL are critical for spermatogenesis, hyperactivation, capacitation, acrosome reaction, and fertilization (Durairajanayagam et al., 2021), and have been associated with semen quality, male fecundity, embryo quality, and in vitro fertilization success (Rocca et al., 2016;Rosati et al., 2020;Wu et al., 2019;Yang et al., 2015b), no toxicological or population study to date has investigated the potential influence of THM exposure on sperm mtDNAcn and TL. ...
... Finally, the link among nutrition, epigenetic changes and CVD predisposition is well supported by several studies that underlined the contribution of an adverse intrauterine environment to impaired fetal growth, glucose/lipid metabolism, early development of atherosclerosis and adult CVD [111,112]. Notably, maternal obesity, high gestational weight gain and gestational diabetes all lead to methylation changes in both placental and fetal DNA and are associated with increased birthweight and with cardiometabolic disease in early childhood [113][114][115][116]. In particular, a high association between specific CpG methylation in offspring (876 female-specific and 293 male-specific CpG sites) and maternal prepregnancy obesity has emerged from the analysis of data from the NEST cohort. ...
... We investigated whether CpG sites associated with childhood anthropometrics, as identified by our recent systematic review [60], were associated with RWG by a look-up of these hits (N=1526 CpGs) in our study population. Results were considered significant if p Bonferroni < 3.28e−05 (0.05/1526). ...
... While the metabolomic profile in adults with obesity has been extensively investigated, the number of clinical studies performing metabolomic analyses in children and adolescents with obesity is limited, as evidenced in the systematic review by Handakas et al. [11]. In particular, when considering a pediatric population, despite wide differences in sample processing, metabolome coverage and analytical technique, the most consistent associations between anthropometric measurements (e.g., body mass index (BMI)) and metabolites were observed by considering branched-chain amino acids (BCAAs) (positive association), the aromatic amino acids tyrosine and phenylalanine (positive association), and many other amino acids (both positive and negative) [11]. Other groups of metabolites were measured by clinical studies carried out in children and adolescents with obesity, including acylcarnitines (particularly those of shorter chain length), steroid hormones, glycerophospholipids, sphingolipids, polyamines, peptides, purines, and single metabolites from other classes [11]. ...
... In all the cohorts, weight measurements were obtained from obstetric records at birth, while measurements at later times were measured by trained staff (in ALSPAC and GXXI) or measured by trained staff or self-reported from parents (in ENVIRONAGE and EXPOsOMICS) as detailed in Additional file 1: Supplementary Methods [27][28][29][30][31][32][33][34][35][36][37][38]. A two-step prediction approach was used for calculating sex-and age-specific weight at exactly 1 year, using fractional polynomials of age by gender in each cohort, as previously described [46]. Weight gain (WG) at 1 year was calculated as the difference between sex-and age-adjusted WHO-SD scores of birthweight and predicted weight at 1 year. ...
... These negative results do not exclude that other shared environmental factors might play a role in accelerated ageing, for example through epigenetic mechanisms. A recent study in 247 newborns reported that 47 CpGs and 7 between-CpG interactions explained 76% of the observed variance in TL (Wang et al. 2021). Other factors possibly intervening during pregnancy, such as exposure to tobacco or pollution, maternal psychosocial stress, or vitamin D levels have been associated with newborn TL (Rosa et al. 2019;Daneels et al. 2021;Isaevska et al. 2021;Verner et al. 2021). ...
... Although, some recent evidence contradicts the importance of paternal BMI on offspring DNAm (Sharp et al., 2020), perhaps indicating a mutually confounding factor responsible for driving the contribution of paternal BMI. Meanwhile, paternal smoking has been linked to DNAm differences in sperm and infant biology, as has infant exposure to second hand smoke (Kohli et al., 2012;Murphy et al., 2019;Odintsova et al., 2018). ...
... Second, literature has reported that some genic regions are consistently responsive to multiple environmental exposures, which makes identifying a single responsible exposure for altered epigenetic change very difficult. For example, several human epidemiological studies have identified DNA methylation changes in the imprinted gene IGF2 associated with air pollution, Pb, or BPA exposure [59,94,95]. Incidentally, epigenetic profiles at metastable epialleles and imprinted genes are set very early in development, are responsive to maternal environmental cues, and remain stable across tissues over time [96,97], mitigating some of the stability and age-related concerns identified above; but, DNA methylation within these genomic regions is responsive to multiple stressors. ...
... Gene expression levels were measured in the 200 cord blood samples of the ENVIRONAGE cohort participating in the EXPOsOMICS project [34]. Total RNA was extracted using the total RNA miRNeasy mini kit (Qiagen, Venlo, Netherlands) according to the manufacturer's protocol, as detailed previously [39,51]. In brief, samples were quality checked and further hybridized onto Agilent Whole Human Genome 8×60 K microarrays, and microarray signals were detected by an Agilent DNA G2505C Microarray Scanner. ...