Biology of Sex Differences最新文献

{"title":"Decoding sex and gender effects on health: evidence from a nationwide cohort.","authors":"Caroline E Gebhard, Bianca Gysi, Pimrapat Gebert, Nidaa Mikail, Livia Liechti, Patrick R Schmidlin, Adriana Vinzens, Achi Haider, Susan Bengs, Valerie Treyer, Philipp K Buehler, Reto A Schuepbach, Annelies S Zinkernagel, Silvio D Brugger, Dimitri Patriki, Benedikt Wiggli, Jürg H Beer, Andrée Friedl, Raphael Twerenbold, Gabriela M Kuster, Joerg C Schefold, Thibaud Spinetti, Pedro D Wendel-Garcia, Daniel A Hofmaenner, Thomas Scheier, Martin Siegemund, Vera Regitz-Zagrosek, Catherine Gebhard","doi":"10.1186/s13293-026-00888-8","DOIUrl":"10.1186/s13293-026-00888-8","url":null,"abstract":"<p><strong>Background: </strong>Validated tools to assess gender are essential for clinical and population research but remain scarce and unstandardized. Understanding how sociocultural gender interacts with biological sex in shaping disease risk is critical for precision medicine. We aimed to investigate the association of sex and gender with cardiovascular risk factors and common comorbidities, and to refine an existing composite Gender score in a Swiss cohort.</p><p><strong>Methods: </strong>This multicenter prospective study conducted in three tertiary and one regional hospital included outpatients and inpatients with PCR-confirmed SARS-CoV-2 infection (n = 2,690; estimation and internal validation sets) and outpatients with periodontitis (n = 337; external validation set). Gender-related variables were acquired via questionnaire. Logistic regression models and propensity score matching were used to assess associations between sex, gender, and the prevalence of cardiometabolic and chronic health conditions.</p><p><strong>Results: </strong>A total of 3,027 individuals (46.3% women; mean age 45 ± 17 years) were included. The composite Gender Score predicted biological sex with good accuracy (ROC 0.776-0.809). Biological sex was more strongly associated with most cardiometabolic risk factors, stroke, immune disorders, and bone diseases, whereas gender showed limited independent associations. For diabetes, female sex was inversely associated with diabetes prevalence, while a more feminine gender profile was positively associated. These opposing associations persisted after accounting for gender in matched analyses, illustrating that sex and gender may contribute differently to specific metabolic outcomes.</p><p><strong>Conclusion: </strong>Sociocultural variables can accurately approximate biological sex and are differentially associated with health outcomes. In this cohort, biological sex explained most associations with cardiometabolic and chronic conditions, while gender effects were modest and condition-specific. The divergent associations observed for diabetes highlight that sex and gender are related but distinct constructs that should be considered jointly. Integrating both dimensions may improve future approaches to risk stratification, although these findings require confirmation in prospective and diverse populations.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13154686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in congenital hereditary endothelial dystrophy (CHED) and Slc4a11^-/- mouse model of CHED.","authors":"Wenlin Zhang, Divya Sree Ramya, Eduardo Araujo, Jhuwala Venkatakrishnan, Saloni Gupta, Isa Matsubayashi, Marco Morselli, Ananya Kaginalkar, Sunita Chaurasia, Matteo Pellegrini, Radhika Tandon, Muralidhar Ramappa, Arthur Arnold, Anthony J Aldave","doi":"10.1186/s13293-026-00879-9","DOIUrl":"10.1186/s13293-026-00879-9","url":null,"abstract":"<p><strong>Background: </strong>Sex differences have been described in several corneal diseases such as Fuchs endothelial corneal dystrophy and keratoconus, with estrogens implicated in the induction of these differences. Here, we report the identification of sex differences in a cohort of 177 individuals with Corneal Hereditary Endothelial Dystrophy (CHED), a rare corneal endothelial dystrophy associated with biallelic SLC4A11 gene mutations, and in a Slc4a11^-/- mouse model of CHED.</p><p><strong>Methods: </strong>Central corneal thickness (CCT) was measured in individuals with CHED and in Slc4a11^-/- and Slc4a11^+/+ mice to identify a correlation between sex and the degree of corneal edema. To investigate potential causes of such a correlation, RNAseq analysis and mitochondrial superoxide measurement were performed on corneal endothelium from male and female Slc4a11^-/- and Slc4a11^+/+ mice, for which body composition analysis was also performed. Gonadectomy or sham surgery was performed in Slc4a11^-/- and Slc4a11^+/+ mice at 4 weeks of age with subsequent longitudinal CCT and body weight monitoring, followed by an analysis of the interaction effect of surgery type, sex and genotype on CCT.</p><p><strong>Results: </strong>Male sex is associated with increased CCT, and thus more severe corneal edema, the characteristic clinical feature of CHED, in affected individuals and Slc4a11^-/- mice. The corneal endothelium in male Slc4a11^-/- mice demonstrates increased levels of oxidative stress compared to Slc4a11^-/- female mice, as evidenced by higher levels of glucose- and glutamine-derived mitochondrial superoxide, controlling for age. Removal of gonadal hormones in Slc4a11^-/- mice increases corneal edema in female mice, suggesting a protective role for ovarian hormones. Transcriptomic analysis of corneal endothelium and body composition analysis in Slc4a11^+/+ and Slc4a11^-/- mice suggest that estrogens play a role in promoting corneal endothelial utilization of lipids via β-oxidation as an alternative energy source in the absence of SLC4A11-mediated NH₃:H transport function, thereby reducing oxidative stress from glucose and glutamine metabolism.</p><p><strong>Conclusions: </strong>Male sex is associated with a more severe corneal phenotype in individuals with CHED and a Slc4a11^-/- mouse model of the disease. Increased corneal edema in female Slc4a11^-/- mice following gonadectomy suggests ovarian hormones play a protective role in maintaining corneal deturgescence in the setting of loss of SLC4A11 function.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147526095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C16-ceramide modulates sex-dimorphic defense strategies under cold stress in Cherax quadricarinatus via JAK-STAT suppression and oxidative disruption.","authors":"Honglin Chen, Huiyi Cai, Shuzhi Li, Xiaojun Xu, Bao Lou","doi":"10.1186/s13293-026-00892-y","DOIUrl":"10.1186/s13293-026-00892-y","url":null,"abstract":"<p><strong>Background: </strong>Extreme low temperatures impose severe physiological stress on aquatic crustaceans. Understanding the molecular mechanisms of cold adaptation is critical for improving stress resilience in key aquaculture species. This study employed integrated transcriptomic and metabolomic analyses to decipher sex-divergent neuroendocrine strategies in Cherax quadricarinatus under cold stress.</p><p><strong>Results: </strong>Males rely on high basal antioxidant capacity for rapid JAK-STAT pathway activation to combat acute cold stress, whereas females maintain metabolic homeostasis through sustained pathway activation. This sexually dimorphic strategy is negatively regulated by C16-ceramide. Females relied on sustained JAK-STAT activation for transcriptional reprogramming, while males exhibited rapid metabolic remodeling and transient antioxidant mobilization. Crucially, the sphingolipid hub molecule C16-ceramide was coordinately downregulated in both sexes. Exogenous supplementation revealed C16-ceramide potently suppressed JAK-STAT genes and disrupted hepatopancreatic redox homeostasis in females, while triggering antioxidant collapse in males.</p><p><strong>Conclusions: </strong>This study provides the first evidence of sexual dimorphism in JAK-STAT mediated cold adaptation in invertebrates, identifies C16-ceramide as a regulator of sex-specific defense strategies, and confirms the penetration of sexual dimorphism into conserved molecular stress response networks.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific changes in the hippocampal proteome of Negr1^-/- mice: insight into the mechanisms of neuropsychiatric disorders.","authors":"Srirathi Muthuraman, Mohan Jayaram, Liisi Promet, Toomas Jagomäe, Arun Kumar Devarajan, Andreas-Christian Hade, Mari-Anne Philips, Katyayani Singh, Eero Vasar","doi":"10.1186/s13293-026-00890-0","DOIUrl":"10.1186/s13293-026-00890-0","url":null,"abstract":"<p><p>BACKGROUND: Neuronal Growth Regulator 1 (NEGR1) is a cell adhesion molecule involved in hippocampal circuit development and function. Human genetic studies have identified NEGR1 variants as risk factors for a broad spectrum of neuropsychiatric disorders. These disorders often display sex-specific differences in prevalence, progression, and behavioral impairment, reflecting underlying maladaptive changes in neural circuitry. Findings from preclinical studies using Negr1−/− mice show several hippocampal-based behavioral and anatomical endophenotypes relevant to neuropsychiatric disorders. The hippocampus, a key region implicated in these disorders, exhibits sex-dependent anatomical features that may shape the functional impact of Negr1. However, the mechanisms driving these sex-specific characteristics have not yet been elucidated. Here, we uncover sex-specific molecular signatures and pathways associated with Negr1, using Negr1−/− mice, a genetically relevant animal model for neuropsychiatric risk. METHODS: We performed label-free quantitative proteomic analysis using eight replicates of hippocampi dissected from male and female wild-type, and Negr1−/− mice. Differentially abundant proteins were subjected to functional annotation for Gene Ontology and Protein-Protein interaction using STRING analysis. NEGR1 cellular localization was examined by immunofluorescent in rat brain and human hippocampal sections. RESULTS: Differential expression analysis identified 232 proteins in males and 172 in females. STRING analysis revealed sex-specific regulation of proteins. In males, proteins linked to neurofilament organization, myelin integrity, and postsynaptic structure were downregulated, with parvalbumin (Pvalb, PV) around the central node. In contrast, proteins related to mitochondrial and stress-response pathways were upregulated. Female Negr1−/− hippocampus showed downregulation of proteins involved in translation and amide biosynthetic processes. Colocalization of NEGR1 with PV interneurons in the rat brain and the human hippocampus was observed. CONCLUSIONS: We demonstrate, for the first time, distinct sex differences in the hippocampal proteome and identify molecular networks in Negr1−/− mice. Co-localization of NEGR1 and PV in human brain tissue provides anatomical and translational validation of a proteomic target. These findings provide new insight, offering a valuable resource for understanding NEGR1-related sex-specific mechanisms in neuropsychiatric disorders.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the clinical outcomes of chronic hepatitis B infection among paediatric patients.","authors":"Wenxian Ouyang, Zhenzhen Yao, Yingping Gu, Xin Lai, Songxu Peng","doi":"10.1186/s13293-026-00826-8","DOIUrl":"10.1186/s13293-026-00826-8","url":null,"abstract":"<p><strong>Background: </strong>The impacts of sex on treatment response in paediatric patients with chronic hepatitis B virus (HBV) infection remains incompletely understood. We aimed to analyse sex differences in antiviral treatment response in children with HBV infection.</p><p><strong>Methods: </strong>We performed a retrospective cohort study on 236 treatment-naive children with chronic HBV infection at the Liver Disease Centre of Hunan Children's Hospital. The Cox proportional hazard regression was used to estimated treatment outcome differences between males and females.</p><p><strong>Results: </strong>Of the 236 subjects, the median age at treatment initiation was 4 (2,7) years, and 155 (65.68%) were male. After the median follow-up (IQR) of 27 (18, 43) months, the crude cumulative incidence of HBsAg loss, HBeAg clearance and HBV DNA undetectability in patients were 48.73%, 61.02% and 89.36%, respectively. Kaplan-Meier curve showed that female patients were more likely to achieving HBsAg loss compared to male patients (58.02% vs. 43.87%, P_log-rank=0.001). After adjustment for other covariates, female sex was significantly associated with the higher possibility of HBsAg loss (female vs. male: Adjusted HR: 2.03, 95% CI: 1.35-3.06) in children with chronic HBV infection. Furthermore, the landmark analysis revealed that the relationship between sex and HBsAg loss became more pronounced beyond the first year (female vs. male: adjusted HR (95%CI): 2.18(1.29-3.69)).</p><p><strong>Conclusion: </strong>Children with chronic HBV infection receiving antiviral treatment are frequently observed to achieve functional cure. Sex plays an important role in treatment response among paediatric patients, with female patients exhibiting a higher likelihood of achieving HBsAg loss, particularly after one- year of follow-up.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13141448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The persisting presence of absence in female sex development: a critical interdisciplinary reflection.","authors":"Birgit Stammberger, Xenia Steinbach, Nadine Hornig","doi":"10.1186/s13293-026-00848-2","DOIUrl":"10.1186/s13293-026-00848-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;For much of the 20th-century, developmental endocrinology was structured around a binary model that positions male differentiation as an active, hormone-driven process and female development as the passive consequence of androgen absence. This framework has profoundly shaped both experimental practice and conceptual understanding in reproductive and developmental biology. Yet, empirical evidence in molecular endocrinology, combined with insights from feminist science studies and the history of science, invites a revitalization of the long-standing critique of the persistence of this model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main body: &lt;/strong&gt;This review critically re-interrogates the longstanding notion of female sex development as an outcome of mere androgen deprivation. First, through a historical analysis of key experimental systems in 20th-century embryological endocrinology, we trace how this conceptual pattern emerged and became stabilized within the discipline. We show how the methodological privileging of androgenic mechanisms over other hormonal pathways contributed to defining femaleness as absence. Second, drawing on research in developmental and molecular endocrinology, we review the roles of oestrogens and their receptors in mammalian female genital development. Synthesizing these findings, we support a less reductionist model that opens the possibility to more research on oestrogen-dependent female sex differentiation and defines female sex development as an active, regulated process rather than a default state. Finally, we situate the 'absence' model of femaleness within its broader cultural and symbolic contexts. Through a material-semiotic analysis, we demonstrate how scientific concepts of sex are co-constituted with wider social meanings, and how this interplay shapes what is rendered visible or invisible in biological research.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Emerging from a multidisciplinary dialogue between biomedicine, the history of science, and feminist science studies, our review highlights how cultural assumptions of gender are embedded within scientific practices of analyzing sex-differences. By integrating reflexive humanities perspectives with empirical biomedical research, we argue for a more accurate and equitable understanding of female development - one that recognizes oestrogenic activity as central to sex differentiation and challenges the reduction of femaleness to hormonal absence. This cross-disciplinary engagement illustrates the transformative potential of re-examining foundational scientific paradigms through collaborative, critical inquiry. Research on how sex develops in mammals was based for a long time on a simple binary model: male development is an active process driven by androgens, while female development happens passively when these hormones are absent. Our article re-challenges this long-standing view by referring to the history of the concept of female sex development as a pass","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in the strategies of haptic object memory in early adulthood.","authors":"Lea Fröscher, Matthias W Riepe","doi":"10.1186/s13293-026-00880-2","DOIUrl":"10.1186/s13293-026-00880-2","url":null,"abstract":"<p><p>Everyday life inevitably involves touch. Encoding, recalling, and recognizing objects by touch requires haptic object memory, which is thought to rely on both verbal and visual capabilities. This raises the question of whether performance or strategies used to solve haptic memory tasks are sex-dependent. We assessed 45 healthy young adults (27 females, 18 males; aged 18-36 years) with repeated measurements. Participants were asked to encode ten everyday objects while blindfolded and allowed to explore them by touch. After a five-minute delay, participants were asked to recall as many objects as possible and subsequently to recognize the objects from a set of five conceptually identical but perceptually different alternatives with their eyes open. Regardless of whether participants correctly identified the object, they were then allowed to touch it. Performance did not differ between women and men in all memory phases. However, men appeared to rely less on verbal memory and instead used mental rotation as a compensatory strategy during encoding. Women who in this sample showed better verbal memory performance, did not require such backup strategies for encoding. During the recognition task, the results suggest that men may have relied on mental rotation, whereas women may have favored verbal strategies. These findings indicate a tendency toward different strategy preferences rather than fixed sex-specific mechanisms. However, given the modest sample size, these findings should be interpreted cautiously and warrant replication in larger cohorts. Nonetheless, we conclude that when task demands increase, men may compensate by engaging mental object rotation.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific associations of SHBG, testosterone, and obesity with cholecystectomy risk: a population-based cohort study.","authors":"Jie-Qiong Lyu, Yi Luo, Yu-Wen Qian, Ji-Mei Gu, Meng-Yuan Miao, Guo-Chong Chen, Guo-Jian Yin","doi":"10.1186/s13293-026-00884-y","DOIUrl":"10.1186/s13293-026-00884-y","url":null,"abstract":"<p><strong>Background: </strong>Gallstone disease exhibits a marked sex difference. While obesity and female sex hormones are known risk factors, the role of sex hormone-binding globulin (SHBG) and testosterone in gallstone-related risk, and whether they mediate the association between obesity and gallbladder disease, remain unclear.</p><p><strong>Methods: </strong>We included 176,909 men and 160,147 women from the UK Biobank. Serum SHBG and testosterone were measured using immunoassays. Incident cholecystectomy cases were identified through hospital records. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Mediation analyses were performed to assess the contribution of SHBG and testosterone to the obesity-cholecystectomy association.</p><p><strong>Results: </strong>A total of 2,877 men and 4,607 women underwent cholecystectomy. Higher SHBG levels were associated with a lower risk of cholecystectomy in both sexes, with a stronger association in women (HR_{Q4 vs. Q1} = 0.40, 95% CI: 0.36-0.43) than in men (HR_{Q4 vs. Q1} = 0.67, 95% CI: 0.59-0.77). Elevated testosterone levels were associated with an increased risk of cholecystectomy only in women (HR_{Q4 vs. Q1} = 1.28; 95% CI: 1.18-1.38). Obesity exhibited a stronger association with cholecystectomy in women than in men. In women, SHBG mediated 14.7% and 20.0% of the associations between general and abdominal obesity and cholecystectomy, respectively, whereas testosterone mediated smaller proportions (2.7% and 1.8%). No significant mediation was observed in men.</p><p><strong>Conclusions: </strong>SHBG levels are inversely associated with risk of cholecystectomy in both sexes, whereas higher testosterone levels are associated with a higher risk of cholecystectomy only in women. SHBG and, to a lesser extent, testosterone accounted for a modest proportion of the obesity-cholecystectomy association in women.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific dynamics of MASLD reveal early hepatic and extrahepatic metabolic deterioration in females despite long-term protection.","authors":"Maria Repollés-de-Dalmau, Anna Marsal-Beltran, Catalina Núñez-Roa, Joan Vendrell, Victòria Ceperuelo-Mallafré, Sonia Fernández-Veledo","doi":"10.1186/s13293-026-00876-y","DOIUrl":"10.1186/s13293-026-00876-y","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition characterized by hepatic fat accumulation and systemic metabolic dysfunction. MASLD exhibits clear sex differences, yet the mechanisms underlying these disparities remain poorly defined.</p><p><strong>Methods: </strong>To investigate the early temporal dynamics of MASLD, male and female mice were fed a choline-deficient, methionine-restricted (0.1%) high-fat (61%) diet (CDAHFD; characterized by impaired hepatic lipid export and enhanced lipotoxic stress) for two weeks, enabling assessment of initial metabolic responses.</p><p><strong>Results: </strong>Despite their presumed protection, females developed an exacerbated hepatic phenotype accompanied by intestinal remodeling and compromised barrier integrity. In contrast, males displayed early weight loss and improved glucose tolerance, alongside reduced hepatic transcriptional changes indicative of adaptive metabolism. Additionally, sex-specific hypothalamic responses were observed, with males showing reduced expression of microglial homeostatic markers, increased inflammation, and alterations in energy balance-related signaling, consistent with neuroimmune modulation. These responses were paralleled by sex-dependent alterations in adipose tissue, including early adipocyte remodeling and distinct transcriptional changes, which were predominantly consistent with baseline sex differences and therefore suggest a limited contribution of this tissue to the early diet-induced metabolic divergence. Importantly, these early sex-dependent adaptations were not sustained over time, as prolonged CDAHFD (14 weeks) resulted in a shift towards a more sever inflammatory and fibrotic hepatic phenotype in males, while females exhibited relative preservation of hepatic metabolic function and attenuation of intestinal alterations.</p><p><strong>Conclusions: </strong>These findings demonstrate that sexual dimorphism in MASLD arises early and evolves dynamically, with females mounting an acute metabolic and intestinal stress response, whereas males activate compensatory pathways that preserve metabolic homeostasis. These results highlight sex-specific trajectory in MASLD progression and emphasize the need for integrative approaches to unravel its pathophysiology.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological sex, but not obesity, independently predicts anatomical injury patterns in trauma bay patients: a multivariate retrospective analysis of 2,128 patients.","authors":"C Pietsch, B Erdle, F Klingler, F C Wagner, J P Maier, H Schmal, N Mühlenfeld","doi":"10.1186/s13293-026-00883-z","DOIUrl":"10.1186/s13293-026-00883-z","url":null,"abstract":"<p><strong>Background: </strong>While sex-specific disparities in trauma outcomes are well established; the biological contribution of sex versus anthropometric variables like obesity in determining initial anatomical injury severity remains poorly understood. This study aimed to independently isolate the effect of biological sex on serious damage, while controlling for energy exposure and body factors.</p><p><strong>Methods: </strong>A retrospective cohort study of 2,128 consecutive adult trauma bay patients (males: n = 1570; females: n = 558) was conducted. Univariate comparisons and multivariate binary logistic regression models were used to identify independent predictors of severe overall injury (Injury Severity Score [ISS] ≥ 9) and severe regional injuries (Abbreviated Injury Scale [AIS] ≥ 3), while controlling for age, body-mass-index (BMI) and obesity (BMI ≥ 30). Adjusted odds ratios (aOR) were calculated with 95% confidence intervals.</p><p><strong>Results: </strong>Compared to females, males were significantly more likely to suffer High-Energy Trauma (HET) (p < 0.001) and had a higher overall injury severity (ISS ≥ 9) in univariate analysis. Male sex was found to be an independent predictor of significant injury in all adjusted models: ISS ≥ 9 (aOR = 1.33, p = 0.010), AIS ≥ 3 for thorax/spine (aOR = 1.38, p = 0.003), and AIS ≥ 3 for face (aOR = 1.78, p = 0.020). For ISS ≥ 9 (aOR = 1.27, p = 0.034) and AIS ≥ 3 thorax/spine (aOR = 2.40, p < 0.001), HET was an independent predictor. Neither dichotomous obesity (BMI ≥ 30) nor continuous BMI was a significant independent predictor of any injury outcome (all p ≥ 0.075), with odds ratios near unity (OR range: 0.978-1.017) indicating no dose-response relationship.</p><p><strong>Conclusions: </strong>Biological sex and kinetic energy are the primary determinants for severe overall and regional trauma. Conversely, obesity does not independently affect initial anatomical injury severity. The lack of independent impact from obesity suggests that sexual dimorphism in biomechanics, skeletal geometry, and tissue resilience - rather than absolute obesity - underlies the increased vulnerability of males in acute trauma.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}