Physiological genomics最新文献

{"title":"Dysbiosis in PCOS: a systematic review of microbiome alterations across body sites with GRADE assessment of evidence quality.","authors":"Navjot Kaur, Nisha Yadav, Sarika Sachan, Priya Sharma, Preeti Khetarpal","doi":"10.1152/physiolgenomics.00072.2025","DOIUrl":"10.1152/physiolgenomics.00072.2025","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine-metabolic disorder that adversely affects reproductive, metabolic, and cardiovascular health in females, leading to menstrual irregularities and an increased risk of endometrial malignancies. Emerging research evidence suggests that the gut and extra gastrointestinal microbiome dysbiosis may play a significant role in the pathophysiology of PCOS. This systematic review aims to elucidate the microbiome dysbiosis patterns in patients with PCOS compared with healthy controls. A systematic search was conducted across PubMed, Scopus, and Web of Science from inception until February 28, 2025, encompassing all original cross-sectional, cohort, or case-control studies that examined the gut, oral, blood, and lower genital tract (LGT) microbiomes of patients with PCOS (cases) against healthy females (controls). Of the 4,377 studies identified, 64 were assessed for eligibility through full-text screening, and ultimately, 29 studies met inclusion criteria and were included into the systematic review. The results revealed inconsistent patterns in alpha and beta diversity, with reports of increased, decreased, or unchanged microbial diversity across studies. Key alterations were observed at different taxonomic levels, such as phylum, family, genus, and species. The most significant bacterial alterations include changes in the relative abundance of various bacterial taxa such as <i>Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, Verrucomicrobia, Gammaproteobacteria, Fusobacteria, Eubacterium, Streptococcus, Paraprevotella, Tucibacter,</i> and <i>Tenericutes</i>. These findings indicate that complex dysbiotic microbial shifts may be involved in the pathogenesis of PCOS. As per the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment, the quality of evidence is low for most of the studies. This systematic review supports the role of microbial dysbiosis in PCOS pathogenesis; however, additional research is required to elucidate these interactions to guide the development of therapeutic strategies in the future.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"667-681"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding exercise adaptation through multidimensional biocircuitry.","authors":"Jacob M Haus, Andrew T Ludlow","doi":"10.1152/physiolgenomics.00195.2025","DOIUrl":"10.1152/physiolgenomics.00195.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"697-699"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross talk between obesogenic diet and estrogen drives distinct microbiota profiles in ovariectomized mice.","authors":"Taylor B Scheidl, Jessica L Wager, Jane Shearer, Jennifer A Thompson, Chunlong Mu","doi":"10.1152/physiolgenomics.00184.2025","DOIUrl":"10.1152/physiolgenomics.00184.2025","url":null,"abstract":"<p><p>The menopausal transition is associated with an increased risk of obesity, which can be ameliorated by hormone replacement therapy. However, the independent and interactive effects of obesity and menopause on the gut microbiota, along with the influence of hormone therapy, remain poorly understood. To address this, this study used a mouse model using sham-operated and ovariectomized mice, with or without high-fat diet-induced obesity, to disentangle the roles of menopause and obesity. Ovariectomized mice on a high-fat diet were further treated with estradiol to assess the regulatory effects of hormone supplementation on the gut microbiota. The results showed that obesity and ovariectomy altered the relative abundances of 29 and 7 genera, and 243 and 99 amplicon sequence variants, respectively, indicating a stronger impact of obesity on gut microbial composition. Notably, ovariectomy increased the abundance of <i>Faecalibaculum</i> and enriched microbial taxa capable of producing estrogen-metabolizing enzymes, including <i>Bifidobacterium</i> and <i>Dubosiella</i> species, as well as the predicted abundance of the estrobolome enzyme β-glucuronidase. Estradiol supplementation increased the relative abundance of <i>Bacteroides</i> and decreased <i>Akkermansia</i>, both of which possess distinct β-glucuronidase subtypes. It also reduced the species <i>Faecalibaculum rodentium</i>, that positively associated with adiposity. Together, these findings highlight the distinct and significant impacts of obesity and menopause on the gut microbiota and suggest that estrogen supplementation modulates microbial features linked to metabolic health. These results further implicate the potential of modulating the gut microbiota to improve postmenopausal health outcomes.<b>NEW & NOTEWORTHY</b> This study investigates how obesity, menopause, and estrogen supplementation influence the gut microbiota. The findings highlight the distinct and significant effects of obesity and menopause in shaping microbial composition and suggest that estrogen supplementation modulates microbial features associated with metabolic health.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"734-743"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Getting to the heart of RNAlligator.","authors":"Otto J Mulleners, Bjarke Jensen","doi":"10.1152/physiolgenomics.00162.2025","DOIUrl":"10.1152/physiolgenomics.00162.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"695-696"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145421983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular phenotypes in early gallbladder and liver disease in the <i>CFTR</i>^-/- sheep highlight aspects of cystic fibrosis-relevant hepatobiliary disease.","authors":"Frederick Meckler, Arnaud J Van Wettere, Ayushi Umrigar, Gurkan Bebek, Shih-Hsing Leir, Iuri Viotti Perisse, Katreya Lovrenert, Kenneth L White, Irina A Polejaeva, Ann Harris","doi":"10.1152/physiolgenomics.00208.2025","DOIUrl":"10.1152/physiolgenomics.00208.2025","url":null,"abstract":"<p><p>The initiating cellular events in cystic fibrosis (CF) hepatobiliary disease are not well characterized, in part due to the lack of accessibility of primary tissues. However, enhanced longevity due to highly effective modulator therapies has generated renewed interest in the key aspects of liver and gallbladder disease, and how these might be treated in people with cystic fibrosis (pwCF). To extend the CF hepatobiliary knowledge base, we performed a transcriptomic analysis of liver and gallbladder development in the wild-type (WT) and <i>CFTR^-/-</i> sheep. Bulk RNA was extracted from each tissue at specific timepoints through gestation (from 50 days to term) and used for RNA sequencing (RNA-seq). Differentially expressed genes between the timepoints within each genotype and between WT and <i>CFTR^-/-</i> sheep at each timepoint were identified and then used in gene ontology process enrichment analysis to reveal altered biological processes. We find that at the molecular level, the gallbladder in the <i>CFTR^-/-</i> animals is both structurally and functionally compromised by midgestation, consistent with the observed microgallbladder phenotype. In the liver, many aspects of differentiation are apparently well-established early in gestation. However, we find functional immaturity in the <i>CFTR^-/-</i> liver at term, where genes associated with many key metabolic processes do not show the upregulation seen at term in the WT liver. We also show that the regulatory mechanisms for the <i>CFTR</i> gene in ovine gallbladder cells are highly conserved with those elucidated at the human <i>CFTR</i> locus, further enhancing the relevance of these data to advance understanding of hepatobiliary disease in pwCF.<b>NEW & NOTEWORTHY</b> We use a physiological genomics approach to further understand the etiology of cystic fibrosis gallbladder and liver disease by using a large animal (sheep) model of organ development. We find that the gallbladder in the <i>CFTR^-/-</i> animals is both structurally and functionally compromised by midgestation. We also observe functional immaturity in the <i>CFTR^-/-</i> liver at term, where genes associated with many key metabolic processes do not show the upregulation seen at term in wild-type liver.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"682-694"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing reveals genes relevant to periodontal therapy and periodontitis.","authors":"Rei Sekiguchi, Daniel Martin, Kenneth M Yamada","doi":"10.1152/physiolgenomics.00002.2025","DOIUrl":"10.1152/physiolgenomics.00002.2025","url":null,"abstract":"<p><p>Periodontal therapy leverages intercellular and intertissue interactions between epithelium and stroma, which mediate healing and regeneration. Importantly, grafting stroma from different regions elicits different healing responses: transplantation of gingival stroma can convert alveolar mucosa into keratinized gingiva, and vice versa. This striking clinical observation suggests that the stromal tissues of oral mucosa and gingiva provide distinct instructional signals. Our aims were to investigate the molecular differences between mucosa and gingiva and the impact of periodontal infection on intertissue interactions. We used human single-cell RNA-sequencing (RNA-seq) data to compare gene expression patterns and intercellular interactions of: <i>1</i>) adult oral mucosa and gingiva and <i>2</i>) healthy gingiva and periodontitis-affected gingiva. Altered gene expression in junctional epithelial cells in periodontitis included not only inflammatory but also antioxidant genes, reflecting the potential of oral tissues to maintain health and resist bacterial infection. Many ligand/receptor genes were also enriched in junctional epithelium, highlighting intercellular interactions. Oral mucosal and gingival stroma expressed distinct genes related to signaling and extracellular matrix associated with their tissue phenotypes: for example, collagens and secreted protein acidic and cysteine-rich (<i>SPARC</i>) in the gingiva, and elasticity-related coagulation factor XIII A chain (<i>F13A1</i>) in the mucosa. Ligand-receptor analyses predicted endothelial cells and fibroblasts as the primary senders of signaling ligands. Notably, autocrine signaling was predicted to be prevalent within periodontitis-affected fibroblasts, suggesting potential autofeedback regulation in periodontitis. We present unbiased single-cell molecular characterizations of human oral tissues in health and periodontitis. These findings lay the groundwork for future research into periodontal therapies.<b>NEW & NOTEWORTHY</b> To explore differences between oral mucosa and gingiva in health and disease, we analyzed human single-cell RNA-sequencing data. In periodontitis, altered gene expression in junctional epithelium included not only inflammatory but also antioxidant genes, reflecting the potential of oral tissues to resist bacterial infection. Each cell type-fibroblasts, endothelial, and immune cells-expressed genes that distinguished mucosa from gingiva, as well as healthy from diseased gingiva. These findings provide insights into periodontitis and periodontal therapy.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"720-733"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12822488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145377981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connecting genes to physiology: the first 25 years of <i>Physiological Genomics</i>.","authors":"Bina Joe, Allen W Cowley, Michael R Garrett, Alison J Kriegel, Jeremy W Prokop, Elaine C Lee, Oluwatosin M Akinola, Hilary A Coller","doi":"10.1152/physiolgenomics.00207.2025","DOIUrl":"10.1152/physiolgenomics.00207.2025","url":null,"abstract":"<p><p><i>Physiological Genomics</i> (PG) published its first issue in July 1999, with the goal of providing a forum for scientists to exchange ideas and scientific results related to the linkage between genetic information and physiological function. In this review, past and present editors reflect on <i>PG</i>'s role in the scientific community, the founding of the journal and the historical context in which it was formed within the American Physiological Society (APS). The editors reflect on a critical conference that united physiologists and geneticists and their determination for APS to take the lead in integrating these communities. In the past 25 years, key technologies for linking genes to physiology including methods for DNA sequencing, connecting genotype with phenotype, and monitoring gene expression, metabolites, and microbiota have all been revolutionized, creating a dynamic scientific environment that has resulted in highly impactful research across a wide range of fields. As methods, technologies, and data analysis tools have developed, <i>PG</i> has been a consistent forum for sharing cutting-edge research on the latest advances in the rapidly evolving field of linking molecular data to physiological function. This article highlights the key technological advances related to the connection between genes and physiology. The contribution of the journal to the scientific community during the time periods of each of the five Editors-in-Chief are summarized, illuminating key technological approaches featured in PG and scientific questions that were addressed. The article ends with a look forward, describing what the authors anticipate for the future of PG.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"700-719"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145392202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum for McAdam et al., volume 57, 2025, p. 526-550.","authors":"","doi":"10.1152/physiolgenomics.00068.2025_COR","DOIUrl":"10.1152/physiolgenomics.00068.2025_COR","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":"57 11","pages":"664-665"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The transcriptomes of hypothalamic micropunches reveal sex differences in regulatory processes across hibernation in the Arctic ground squirrel.","authors":"Cole K Deal, M Hoshi Sugiura, Kelly L Drew, Cory T Williams","doi":"10.1152/physiolgenomics.00073.2025","DOIUrl":"10.1152/physiolgenomics.00073.2025","url":null,"abstract":"<p><p>Seasonal life-history events, such as migration, hibernation, and reproduction, depend on coordinated physiological changes. In vertebrates, a conserved thyroid hormone-signaling pathway in the hypothalamus is known to trigger many of these seasonal transitions. However, the broader processes and regulators modulating seasonal physiology are poorly defined. Recent research in Arctic ground squirrels (AGS, <i>Urocitellus parryii</i>) revealed that hypothalamic thyroid hormone signaling is activated, and markers of tanycytic remodeling are expressed in late hibernation in anticipation of springtime reproduction. We conducted RNA-sequencing on hypothalamic micropunches encompassing the arcuate nucleus, median eminence, pars tuberalis, and third ventricle in male and female AGS at early and late hibernation. We found substantial sex differences in the hypothalamic transcriptome across hibernation. Functional enrichment analysis of gene expression data revealed an upregulation of processes and pathways related to hormone transport and neurogenesis in females, whereas this was less apparent in males. Transcription factor binding site analysis of differentially expressed genes identified upstream regulators involved in glial cell differentiation, neuronal development, survival, and plasticity. Notably, many of the intersecting genes from these analyses were localized to specialized glial cells (tanycytes) lining the floor and walls of the third ventricle. Our findings support a model in which annual changes in gene expression rely on a progressive remodeling of tanycytes across hibernation. This remodeling may contribute to seasonal changes in neuronal plasticity and function of the hypothalamus, priming the brain in anticipation of shifting physiological demands upon hibernation termination.<b>NEW & NOTEWORTHY</b> We examine how the transcriptome of hypothalamic micropunches changes across the hibernation season. Our analyses uncover sex-specific changes to regulatory processes associated with hormone transport and neurogenesis. Genes linked to these processes and regulators are strongly localized to third ventricle tanycytes, consistent with the key role these cells play in regulating seasonal physiological changes. Our study supports that using sex as a biological variable is essential for understanding the mechanisms underlying seasonal life-history transitions.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"650-663"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12679999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Localization and quantification of placental <i>HDAC9</i> and <i>RGS2</i> during preeclampsia.","authors":"Megan A Opichka, M Christine Livergood, Kirthikaa Balapattabi, McKenzie L Ritter, Curt D Sigmund, Anne E Kwitek, Justin L Grobe, Jennifer J McIntosh","doi":"10.1152/physiolgenomics.00156.2024","DOIUrl":"10.1152/physiolgenomics.00156.2024","url":null,"abstract":"<p><p>Preeclampsia is a multifaceted pregnancy-associated hypertensive disorder that poses a major threat to maternal and fetal health. Though the etiology is not fully understood, syncytiotrophoblast stress is postulated to be a major driver of maternal symptomology. We previously demonstrated that regulator of G protein signaling-2 (<i>RGS2</i>) expression decreases in human preeclamptic placenta and has a transcriptional dependence on histone deacetylase 9 (<i>HDAC9</i>) in trophoblast cells. Furthermore, experimental reductions of <i>Rgs2</i> expression in the mouse fetoplacental unit are sufficient to induce preeclampsia-like features, including placental stress, in C57BL/6J dams. Here, we examined the hypotheses that <i>HDAC9</i> and <i>RGS2</i> are both expressed within syncytiotrophoblasts, that <i>HDAC9</i> and <i>RGS2</i> expression are positively correlated within these cells, and that expression of each is reduced within syncytiotrophoblasts during preeclampsia. <i>HDAC9</i> and <i>RGS2</i> mRNA were localized and quantified in syncytiotrophoblast cells of human placental samples from pregnancies with and without preeclampsia, using laser-capture microdissection and in situ hybridization methods. Expression of <i>Hdac9</i> and <i>Rgs2</i> was similarly localized in the syncytiotrophoblast of the mouse placenta. Throughout, <i>HDAC9</i>/<i>Hdac9</i> and <i>RGS2</i>/<i>Rgs2</i> were detected and positively correlated in syncytiotrophoblasts, but expression of each was substantially reduced during preeclampsia. These results document reduced <i>HDAC9</i> and <i>RGS2</i> expression specifically in syncytiotrophoblast cells during preeclampsia and provide additional correlative support of HDAC9-mediated control of <i>RGS2</i> expression within this population of trophoblasts. This work provides rationale to further explore cell-specific disruptions in <i>HDAC9</i> and <i>RGS2</i> control and function as a cause of syncytiotrophoblast stress and ultimately preeclampsia.<b>NEW & NOTEWORTHY</b> Syncytiotrophoblast stress contributes to the pathogenesis of preeclampsia, but many of the underlying causes remain undetermined. Previous work has implicated the loss of placental HDAC9-mediated Rgs2 transcription in the disorder. Extending these findings, we report that HDAC9 and RGS2 were abundant and localized primarily to syncytiotrophoblast cells of the control placenta. Expression of both targets was attenuated in these cells during preeclampsia and thus may be an underappreciated source of syncytiotrophoblast stress, warranting further investigation.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"629-637"},"PeriodicalIF":2.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12616666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}