Evolution, Medicine, and Public Health最新文献

{"title":"Girls start life on an uneven playing field: Evidence from lowland rural Nepal.","authors":"Akanksha A Marphatia,&nbsp;Naomi S Saville,&nbsp;Dharma S Manandhar,&nbsp;Mario Cortina-Borja,&nbsp;Alice M Reid,&nbsp;Jonathan C K Wells","doi":"10.1093/emph/eoac029","DOIUrl":"https://doi.org/10.1093/emph/eoac029","url":null,"abstract":"<p><strong>Background and objectives: </strong>Evolutionary research on the sex ratio at birth (SRB) has focused on explaining variability within and between populations, and whether parental fitness is maximized by producing daughters or sons. We tested predictors of SRB in a low-income setting, to understand whether girls differ from boys in their likelihood of being born into families with the capacity to invest in them, which has implications for their future health and fitness.</p><p><strong>Methodology: </strong>We used data from a cluster randomized control trial from lowland rural Nepal (16 115 mother-child dyads). We applied principal component analysis to extract two composite indices reflecting maternal socio-economic and reproductive (parity, age) capital. We fitted mixed-effects logistic regression models to estimate odds ratios of having a girl in association with these individual factors and indices.</p><p><strong>Results: </strong>The SRB was 112. Compared to the global reference SRB (105), there were seven missing girls per 100 boys. Uneducated, early-marrying, poorer and shorter mothers were more likely to give birth to girls. Analysing composite maternal indices, lower socio-economic and reproductive capital were independently associated with a greater likelihood of having a girl.</p><p><strong>Conclusions and implications: </strong>In this population, girls start life facing composite disadvantages, being more likely than boys to be born to mothers with lower socio-economic status and reproductive capital. Both physiological and behavioural mechanisms may contribute to these epidemiological associations. Differential early exposure by sex to maternal factors may underpin intergenerational cycles of gender inequality, mediated by developmental trajectory, education and socio-economic status.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":" ","pages":"339-351"},"PeriodicalIF":3.7,"publicationDate":"2022-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40628666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phylogenetic prioritization of HIV-1 transmission clusters with viral lineage-level diversification rates.","authors":"Rachel L Miller,&nbsp;Angela McLaughlin,&nbsp;Richard H Liang,&nbsp;John Harding,&nbsp;Jason Wong,&nbsp;Anh Q Le,&nbsp;Chanson J Brumme,&nbsp;Julio S G Montaner,&nbsp;Jeffrey B Joy","doi":"10.1093/emph/eoac026","DOIUrl":"https://doi.org/10.1093/emph/eoac026","url":null,"abstract":"<p><strong>Background and objectives: </strong>Public health officials faced with a large number of transmission clusters require a rapid, scalable and unbiased way to prioritize distribution of limited resources to maximize benefits. We hypothesize that transmission cluster prioritization based on phylogenetically derived lineage-level diversification rates will perform as well as or better than commonly used growth-based prioritization measures, without need for historical data or subjective interpretation.</p><p><strong>Methodology: </strong>9822 HIV pol sequences collected during routine drug resistance genotyping were used alongside simulated sequence data to infer sets of phylogenetic transmission clusters via patristic distance threshold. Prioritized clusters inferred from empirical data were compared to those prioritized by the current public health protocols. Prioritization of simulated clusters was evaluated based on correlation of a given prioritization measure with future cluster growth, as well as the number of direct downstream transmissions from cluster members.</p><p><strong>Results: </strong>Empirical data suggest diversification rate-based measures perform comparably to growth-based measures in recreating public heath prioritization choices. However, unbiased simulated data reveals phylogenetic diversification rate-based measures perform better in predicting future cluster growth relative to growth-based measures, particularly long-term growth. Diversification rate-based measures also display advantages over growth-based measures in highlighting groups with greater future transmission events compared to random groups of the same size. Furthermore, diversification rate measures were notably more robust to effects of decreased sampling proportion.</p><p><strong>Conclusions and implications: </strong>Our findings indicate diversification rate-based measures frequently outperform growth-based measures in predicting future cluster growth and offer several additional advantages beneficial to optimizing the public health prioritization process.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":" ","pages":"305-315"},"PeriodicalIF":3.7,"publicationDate":"2022-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40554594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of leg length for metabolic health and fitness.","authors":"Meghan K Shirley, Owen J Arthurs, Kiran K Seunarine, Tim J Cole, Simon Eaton, Jane E Williams, Chris A Clark, Jonathan C K Wells","doi":"10.1093/emph/eoac023","DOIUrl":"10.1093/emph/eoac023","url":null,"abstract":"<p><strong>Background and objectives: </strong>Several studies have linked longer legs with favorable adult metabolic health outcomes and greater offspring birth weight. A recent Mendelian randomization study suggested a causal link between height and cardiometabolic risk; however, the underlying reasons remain poorly understood.</p><p><strong>Methodology: </strong>Using a cross-sectional design, we tested in a convenience sample of 70 healthy young women whether birth weight and tibia length as markers of early-life conditions associated more strongly with metabolically beneficial traits like organ size and skeletal muscle mass (SMM) than a statistically derived height-residual variable indexing later, more canalized growth.</p><p><strong>Results: </strong>Consistent with the 'developmental origins of health and disease' hypothesis, we found relatively strong associations of tibia length-but not birth weight-with adult organ size, brain size, SMM and resting energy expenditure measured by magnetic resonance imaging (MRI), dual-energy X-ray absorptiometry and indirect calorimetry, respectively.</p><p><strong>Conclusions and implications: </strong>Building on prior work, these results suggest that leg length is a sensitive marker of traits directly impacting metabolic and reproductive health. Alongside findings in the same sample relating tibia length and height-residual to MRI-measured pelvic dimensions, we suggest there may exist a degree of coordination in the development of long bone, lean mass and pelvic traits, possibly centered on early, pre-pubertal growth periods. Such phenotypic coordination has important implications for fitness, serving to benefit both adult health and the health of offspring in subsequent generations.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"316-324"},"PeriodicalIF":3.7,"publicationDate":"2022-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10701439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple sclerosis and the microbiota: Progress in understanding the contribution of the gut microbiome to disease.","authors":"Hendrik J Engelenburg,&nbsp;Paul J Lucassen,&nbsp;Joshua T Sarafian,&nbsp;William Parker,&nbsp;Jon D Laman","doi":"10.1093/emph/eoac009","DOIUrl":"https://doi.org/10.1093/emph/eoac009","url":null,"abstract":"<p><p>Multiple sclerosis (MS), a neurological autoimmune disorder, has recently been linked to neuro-inflammatory influences from the gut. In this review, we address the idea that evolutionary mismatches could affect the pathogenesis of MS via the gut microbiota. The evolution of symbiosis as well as the recent introduction of evolutionary mismatches is considered, and evidence regarding the impact of diet on the MS-associated microbiota is evaluated. Distinctive microbial community compositions associated with the gut microbiota of MS patients are difficult to identify, and substantial study-to-study variation and even larger variations between individual profiles of MS patients are observed. Furthermore, although some dietary changes impact the progression of MS, MS-associated features of microbiota were found to be not necessarily associated with diet per se. In addition, immune function in MS patients potentially drives changes in microbial composition directly, in at least some individuals. Finally, assessment of evolutionary histories of animals with their gut symbionts suggests that the impact of evolutionary mismatch on the microbiota is less concerning than mismatches affecting helminths and protists. These observations suggest that the benefits of an anti-inflammatory diet for patients with MS may not be mediated by the microbiota per se. Furthermore, any alteration of the microbiota found in association with MS may be an effect rather than a cause. This conclusion is consistent with other studies indicating that a loss of complex eukaryotic symbionts, including helminths and protists, is a pivotal evolutionary mismatch that potentiates the increased prevalence of autoimmunity within a population.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":" ","pages":"277-294"},"PeriodicalIF":3.7,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9211007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40391337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolved resistance to a novel cationic peptide antibiotic requires high mutation supply.","authors":"Alfonso Santos-Lopez, Melissa J Fritz, Jeffrey B Lombardo, Ansen H P Burr, Victoria A Heinrich, Christopher W Marshall, Vaughn S Cooper","doi":"10.1093/emph/eoac022","DOIUrl":"10.1093/emph/eoac022","url":null,"abstract":"<p><strong>Background and objectives: </strong>A key strategy for resolving the antibiotic resistance crisis is the development of new drugs with antimicrobial properties. The engineered cationic antimicrobial peptide WLBU2 (also known as PLG0206) is a promising broad-spectrum antimicrobial compound that has completed Phase I clinical studies. It has activity against Gram-negative and Gram-positive bacteria including infections associated with biofilm. No definitive mechanisms of resistance to WLBU2 have been identified.</p><p><strong>Methodology: </strong>Here, we used experimental evolution under different levels of mutation supply and whole genome sequencing (WGS) to detect the genetic pathways and probable mechanisms of resistance to this peptide. We propagated populations of wild-type and hypermutator <i>Pseudomonas aeruginosa</i> in the presence of WLBU2 and performed WGS of evolved populations and clones.</p><p><strong>Results: </strong>Populations that survived WLBU2 treatment acquired a minimum of two mutations, making the acquisition of resistance more difficult than for most antibiotics, which can be tolerated by mutation of a single target. Major targets of resistance to WLBU2 included the <i>orfN</i> and <i>pmrB</i> genes, previously described to confer resistance to other cationic peptides. More surprisingly, mutations that increase aggregation such as the <i>wsp</i> pathway were also selected despite the ability of WLBU2 to kill cells growing in a biofilm.</p><p><strong>Conclusions and implications: </strong>The results show how experimental evolution and WGS can identify genetic targets and actions of new antimicrobial compounds and predict pathways to resistance of new antibiotics in clinical practice.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"266-276"},"PeriodicalIF":3.3,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Which 'imperfect vaccines' encourage the evolution of higher virulence?","authors":"James J Bull, Rustom Antia","doi":"10.1093/emph/eoac015","DOIUrl":"10.1093/emph/eoac015","url":null,"abstract":"<p><strong>Background and objectives: </strong>Theory suggests that some types of vaccines against infectious pathogens may lead to the evolution of variants that cause increased harm, particularly when they infect unvaccinated individuals. This theory was supported by the observation that the use of an imperfect vaccine to control Marek's disease virus in chickens resulted in the virus evolving to be more lethal to unvaccinated birds. This raises the concern that the use of some other vaccines may lead to similar pernicious outcomes. We examine that theory with a focus on considering the regimes in which such outcomes are expected.</p><p><strong>Methodology: </strong>We evaluate the plausibility of assumptions in the original theory. The previous theory rested heavily on a particular form of transmission-mortality-recovery trade-off and invoked other assumptions about the pathways of evolution. We review alternatives to mortality in limiting transmission and consider evolutionary pathways that were omitted in the original theory.</p><p><strong>Results: </strong>The regime where the pernicious evolutionary outcome occurs is narrowed by our analysis but remains possible in various scenarios. We propose a more nuanced consideration of alternative models for the within-host dynamics of infections and for factors that limit virulence. Our analysis suggests imperfect vaccines against many pathogens will not lead to the evolution of pathogens with increased virulence in unvaccinated individuals.</p><p><strong>Conclusions and implications: </strong>Evolution of greater pathogen mortality driven by vaccination remains difficult to predict, but the scope for such outcomes appears limited. Incorporation of mechanistic details into the framework, especially regarding immunity, may be requisite for prediction accuracy.</p><p><strong>Lay summary: </strong>A virus of chickens appears to have evolved high mortality in response to a vaccine that merely prevented disease symptoms. Theory has predicted this type of evolution in response to a variety of vaccines and other interventions such as drug treatment. Under what circumstances is this pernicious result likely to occur? Analysis of the theory in light of recent changes in our understanding of viral biology raises doubts that medicine-driven, pernicious evolution is likely to be common. But we are far from a mechanistic understanding of the interaction between pathogen and host that can predict when vaccines and other medical interventions will lead to the unwanted evolution of more virulent pathogens. So, while the regime where a pernicious result obtains may be limited, caution remains warranted in designing many types of interventions.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"202-213"},"PeriodicalIF":3.3,"publicationDate":"2022-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9381216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strength is negatively associated with depression and accounts for some of the sex difference: A replication and extension.","authors":"Caroline B Smith,&nbsp;Tom Rosenström,&nbsp;Edward H Hagen","doi":"10.1093/emph/eoac007","DOIUrl":"https://doi.org/10.1093/emph/eoac007","url":null,"abstract":"<p><strong>Background: </strong>Depression occurs about twice as often in women as in men, a disparity that remains poorly understood. In a previous publication, Hagen and Rosenström predicted and found that grip strength, a highly sexually dimorphic index of physical formidability, mediated much of the effect of sex on depression. Striking results like this are more likely to be published than null results, potentially biasing the scientific record. It is therefore critical to replicate and extend them.</p><p><strong>Methodology: </strong>Using new data from the 2013-14 cycle of the National Health and Nutrition Examination Survey, a nationally representative sample of US households (<i>n</i> = 3650), we replicated models of the effect of sex and grip strength on depression reported in Hagen and Rosenström, along with additional potential confounds and a new detailed symptom-level exploration.</p><p><strong>Results: </strong>Overall, the effects from the original paper were reproduced although with smaller effect sizes. Grip strength mediated 38% of the effect of sex on depression, compared to 63% in Hagen and Rosenström. These results were extended with findings that grip strength had a stronger association with some depression symptoms, like suicidality, low interest and low mood than with other symptoms, like appetite changes.</p><p><strong>Conclusions: </strong>Grip strength is negatively associated with depression, especially its cognitive-affective symptoms, controlling for numerous possible confounds. Although many factors influence depression, few of these reliably occur cross-culturally in a sex-stratified manner and so are unlikely to explain the well-established, cross-cultural sex difference in depression. The sex difference in upper body strength occurs in all populations and is therefore a candidate evolutionary explanation for some of the sex difference in depression. <b>Lay summary:</b> Why are women at twice the risk of developing depression as men? Depression typically occurs during social conflicts, such as physical or sexual abuse. Physically strong individuals can often single-handedly resolve conflicts in their favor, whereas physically weaker individuals often need help from others. We argue that depression is a credible cry for help. Because men generally have greater strength than women, we argue that men may be more likely to resolve conflicts using physical formidability and women to signal others for help. We find that higher grip strength is associated with lower depression, particularly symptoms like feeling down or thoughts of suicide and that strength accounts for part of the sex difference in rates of depression.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":" ","pages":"130-141"},"PeriodicalIF":3.7,"publicationDate":"2022-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8935202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40317548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolution of the human healthcare system and implications for understanding our responses to COVID-19.","authors":"Sharon E Kessler, Robert Aunger","doi":"10.1093/emph/eoac004","DOIUrl":"10.1093/emph/eoac004","url":null,"abstract":"<p><p>The COVID-19 pandemic has revealed an urgent need for a comprehensive, multidisciplinary understanding of how healthcare systems respond successfully to infectious pathogens-and how they fail. This study contributes a novel perspective that focuses on the selective pressures that shape healthcare systems over evolutionary time. We use a comparative approach to trace the evolution of care-giving and disease control behaviours across species and then map their integration into the contemporary human healthcare system. Self-care and pro-health environmental modification are ubiquitous across animals, while derived behaviours like care for kin, for strangers, and group-level organizational responses have evolved via different selection pressures. We then apply this framework to our behavioural responses to COVID-19 and demonstrate that three types of conflicts are occurring: (1) conflicting selection pressures on individuals, (2) evolutionary mismatches between the context in which our healthcare behaviours evolved and our globalized world of today and (3) evolutionary displacements in which older forms of care are currently dispensed through more derived forms. We discuss the significance of understanding how healthcare systems evolve and change for thinking about the role of healthcare systems in society during and after the time of COVID-19-and for us as a species as we continue to face selection from infectious diseases.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"10 1","pages":"87-107"},"PeriodicalIF":3.3,"publicationDate":"2022-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10265044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serial passage in an insect host indicates genetic stability of the human probiotic <i>Escherichia coli</i> Nissle 1917.","authors":"Nicolas C H Schröder,&nbsp;Ana Korša,&nbsp;Haleluya Wami,&nbsp;Olena Mantel,&nbsp;Ulrich Dobrindt,&nbsp;Joachim Kurtz","doi":"10.1093/emph/eoac001","DOIUrl":"https://doi.org/10.1093/emph/eoac001","url":null,"abstract":"<p><strong>Background and objectives: </strong>The probiotic <i>Escherichia coli</i> strain Nissle 1917 (EcN) has been shown to effectively prevent and alleviate intestinal diseases. Despite the widespread medical application of EcN, we still lack basic knowledge about persistence and evolution of EcN outside the human body. Such knowledge is important also for public health aspects, as in contrast to abiotic therapeutics, probiotics are living organisms that have the potential to evolve. This study made use of experimental evolution of EcN in an insect host, the red flour beetle <i>Tribolium castaneum,</i> and its flour environment.</p><p><strong>Methodology: </strong>Using a serial passage approach, we orally introduced EcN to larvae of <i>T.castaneum</i> as a new host, and also propagated it in the flour environment. After eight propagation cycles, we analyzed phenotypic attributes of the passaged replicate EcN lines, their effects on the host in the context of immunity and infection with the entomopathogen <i>Bacillus thuringiensis</i>, and potential genomic changes using WGS of three of the evolved lines.</p><p><strong>Results: </strong>We observed weak phenotypic differences between the ancestral EcN and both, beetle and flour passaged EcN lines, in motility and growth at 30°C, but neither any genetic changes, nor the expected increased persistence of the beetle-passaged lines. One of these lines displayed distinct morphological and physiological characteristics.</p><p><strong>Conclusions and implications: </strong>Our findings suggest that EcN remains rather stable during serial passage in an insect. Weak phenotypic changes in growth and motility combined with a lack of genetic changes indicate a certain degree of phenotypic plasticity of EcN.</p><p><strong>Lay summary: </strong>For studying adaptation of the human probiotic <i>Escherichia coli</i> strain Nissle 1917, we introduced it to a novel insect host system and its environment using a serial passage approach. After passage, we observed weak phenotypic changes in growth and motility but no mutations or changes in persistence inside the host.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":" ","pages":"71-86"},"PeriodicalIF":3.7,"publicationDate":"2022-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39939749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune cell type and DNA methylation vary with reproductive status in women: possible pathways for costs of reproduction.","authors":"Calen P Ryan,&nbsp;Meaghan J Jones,&nbsp;Rachel D Edgar,&nbsp;Nanette R Lee,&nbsp;Michael S Kobor,&nbsp;Thomas W McDade,&nbsp;Christopher W Kuzawa","doi":"10.1093/emph/eoac003","DOIUrl":"https://doi.org/10.1093/emph/eoac003","url":null,"abstract":"<p><strong>Background: </strong>Consistent with evolutionarily theorized costs of reproduction (CoR), reproductive history in women is associated with life expectancy and susceptibility to certain cancers, autoimmune disorders and metabolic disease. Immunological changes originating during reproduction may help explain some of these relationships.</p><p><strong>Methodology: </strong>To explore the potential role of the immune system in female CoR, we characterized leukocyte composition and regulatory processes using DNA methylation (DNAm) in a cross-sectional cohort of young (20-22 years old) women differing in reproductive status.</p><p><strong>Results: </strong>Compared to nulliparity, pregnancy was characterized by differential methylation at 828 sites, 96% of which were hypomethylated and enriched for genes associated with T-cell activation, innate immunity, pre-eclampsia and neoplasia. Breastfeeding was associated with differential methylation at 1107 sites (71% hypermethylated), enriched for genes involved in metabolism, immune self-recognition and neurogenesis. There were no significant differences in DNAm between nulliparous and parous women. However, compared to nullipara, pregnant women had lower proportions of B, CD4T, CD8T and natural killer (NK) cells, and higher proportions of granulocytes and monocytes. Monocyte counts were lower and NK counts higher among breastfeeding women, and remained so among parous women.</p><p><strong>Implications: </strong>Our findings point to widespread differences in DNAm during pregnancy and lactation. These effects appear largely transient, but may accumulate with gravidity become detectable as women age. Nulliparous and parous women differed in leukocyte composition, consistent with more persistent effects of reproduction on cell type. These findings support transient (leukocyte DNAm) and persistent (cell composition) changes associated with reproduction in women, illuminating potential pathways contributing to CoR. <b>Lay Summary:</b> Evolutionary theory and epidemiology support costs of reproduction (CoR) to women's health that may involve changes in immune function. We report differences in immune cell composition and gene regulation during pregnancy and breastfeeding. While many of these differences appear transient, immune cell composition may remain, suggesting mechanisms for female CoR.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":" ","pages":"47-58"},"PeriodicalIF":3.7,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39803213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}