Biology of Sex Differences最新文献

{"title":"Sex differences in atrial fibrillation recurrence after catheter ablation: research status and progress.","authors":"Yongzhi Cao, Hao Wang, Chengyu Shi, Yunfei Gu","doi":"10.1186/s13293-026-00914-9","DOIUrl":"10.1186/s13293-026-00914-9","url":null,"abstract":"<p><p>Sex differences in the risk of recurrence after catheter (CA) ablation for atrial fibrillation (AF) have become a focal point of interest in recent years. This narrative review synthesizes the available evidence and, based on published reports, suggests that female patients may have a higher overall risk of postoperative recurrence than male patients, although substantial heterogeneity exists across studies. This is a narrative review and did not follow the methodological framework of a systematic review (e.g., PRISMA diagram, risk-of-bias assessment, and quantitative synthesis). Sex differences are not driven by a single biological factor but arise from the complex interaction of multidimensional factors, including hormonal levels, electrophysiological characteristics, cardiac remodeling, and clinical management. Current research remains constrained by methodological heterogeneity, inconsistent endpoint definitions, and inadequate adjustment for confounders, which undermine the robustness of the conclusions. Future efforts should advance rigorously designed prospective studies to test current hypotheses. On this basis, the development of sex-sensitive, individualized management pathways-encompassing precise preoperative assessment, substrate-guided ablation strategies, and enhanced postoperative follow-up-may help improve long-term outcomes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13285486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810314","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":"Female rats are more vulnerable to binge drinking behavior in an operant self-administration paradigm: implication for transition to alcohol use disorders.","authors":"Jérôme Jeanblanc, Amélie Soyer, Mickaël Naassila","doi":"10.1186/s13293-026-00912-x","DOIUrl":"10.1186/s13293-026-00912-x","url":null,"abstract":"<p><p>While binge drinking can significantly impact health negatively, it has become increasingly important to understand how sex differences contribute to this hazardous behavior, which may also serve as a risk factor for alcohol use disorder. We employed the binge drinking experimental model we developed previously to specifically analyze sex differences. Forty male and 40 female Long Evans rats were tested in the alcohol self-administration procedure, operationalized as alcohol responding in short daily session. We tested other parameters, including motivation, seeking, responses during cue omission sessions, withdrawal scores, and relapse after abstinence. We also conducted experiments to assess perseverance despite satiety. For the analysis we used first an unsupervised clustering approach using drinking speed and frequency of alcohol responses and then we analyzed our data by taking sex as the differentiating factor. Unbiased clustering analysis revealed four distinct groups: Fast Bingers, Bingers, Extreme Bingers and Low drinkers. Higher alcohol consumption and faster consumption speed correlated with elevated withdrawal scores. Sex-related differences were observed, with females outnumbering males in Extreme bingers. Females also exhibited higher alcohol-seeking behavior, relapse rates, and withdrawal scores. In addition, females exhibit lower sensitivity to devaluation in the satiety test. Our results suggest that females display greater vulnerability to cue-mediated alcohol-seeking behaviors and a more inflexible behavior. This underscores the importance of considering sex as a biological variable in both preclinical and clinical research on binge drinking behaviors that is not only a hazardous behavior but may also be a critical factor in AUD vulnerability, particularly in females.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760749","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 cancer incidence persist across race and ethnicity.","authors":"Julia J Francis, Hormuzd A Katki, Barry I Graubard, Christopher A Haiman, Loïc Le Marchand, Veronica Wendy Setiawan, Lynne R Wilkens, Anil Chaturvedi, Sarah S Jackson","doi":"10.1186/s13293-026-00902-z","DOIUrl":"10.1186/s13293-026-00902-z","url":null,"abstract":"<p><strong>Background: </strong>Males have a higher incidence of cancers at shared anatomic sites than females. We investigated whether sex differences in cancer incidence differed across race/ethnicity.</p><p><strong>Methods: </strong>Within the Multiethnic Cohort Study, we examined the association between sex and cancer incidence at 13 shared anatomic sites using Cox proportional hazards regression to estimate male-to-female hazard ratios (MF HRs) adjusting for cancer specific risk factors by race/ethnic group: African American, Japanese American, Native Hawaiian, Latino, and White. Statistical differences in the MF HRs by race/ethnicity for each site were assessed with an interaction term. The percentage of sex difference in cancer incidence that was statistically explained by the risk factors within race/ethnicity were quantified using a Peters-Belson approach.</p><p><strong>Results: </strong>Of the 178,036 participants, 46% were male and 54% were female. Adjusting for multiple risk factors did not eliminate the MF differences for any of the cancers examined. We found significant differences in MF HRs across race/ethnicity for cancers of the esophagus (Native Hawaiian MF HR 17.67, 95% CI 2.21-141.20; African American 1.28 0.69-2.36; P = 0.018), liver (Japanese American 1.28, 0.96-1.70; White 2.79, 1.81-4.30, P = 0.005) and thyroid (Latino 0.21, 0.13-0.35; White 0.83, 0.50-1.37, P = 0.005). Cancer risk factors explained 82% of the overall sex difference observed for lung cancer but 0% of the difference for gallbladder cancer.</p><p><strong>Discussion: </strong>Most non-sex-specific cancers have male predominance across race/ethnicity, which are not fully explained by cancer risk factors, suggesting there may be intrinsic sex differences driving these differences in cancer incidence.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760457","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":"Intranasal Galanin(1-15) influences depression- and anxiety-related behaviors through sex-dependent mechanisms in rats.","authors":"Noelia Cantero-García, Antonio Flores-Burgess, Marta Flores-Gómez, Juan Pedro Pineda-Gómez, Carmelo Millón, Zaida Díaz-Cabiale","doi":"10.1186/s13293-026-00901-0","DOIUrl":"10.1186/s13293-026-00901-0","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder affects more women than men, possibly due to sex-specific biological and environmental factors. Previous studies have shown that Galanin, as well as specific fragments of it, such as Galanin 1-15 [GAL(1-15)], play a crucial role in modulating depression in animal models by acting on brain regions like the hippocampus and dorsal raphe nuclei. Until now, its effects had only been studied in male rats, where GAL(1-15) produces depressive and anxiogenic behaviors in behavioral tests. This study analyzes, for the first time, the effects of GAL(1-15) on female rats and compares the expression of galaninergic and serotonergic genes between males and females to understand sex-dependent mechanisms in depression.</p><p><strong>Methods: </strong>For this purpose, the effect of GAL(1-15) administered intranasally in female rats was assessed, using validated behavioral tests for depression: the Forced Swim Test (FST) and the Tail Suspension Test (TST), as well as the anxiety behavior test: the Open Field Test (OFT). Furthermore, the expression of galaninergic genes (GAL, GALR1, GALR2, GALR3) and the 5-HT1A receptor was compared in untreated male and female rats using qPCR in key brain regions implicated in depressive disorder: the dorsal raphe nucleus (DR), the dorsal hippocampus, and the prefrontal cortex (PFC).</p><p><strong>Results: </strong>We demonstrated that GAL(1-15) intranasally administered in female rats strongly produced depressive behavior in the FST as well as in the TST. Moreover, in the anxiety test, intranasal GAL(1-15) at high doses produced anxiety behavior in the OFT. In addition, the qPCR study revealed that naïve female rats exhibited increased expression of the galaninergic system and 5-HT1A receptor compared to naïve male rats in the DR, dorsal hippocampus, and PFC, several nuclei implicated in depression.</p><p><strong>Conclusions: </strong>These results demonstrate the existence of sexual dimorphism in the galangergic system.These findings on sex-specific neurobiological variations are crucial for advancing toward more precise therapies tailored to the specific characteristics of each sex in the treatment of depression.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13261986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760524","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":"Capturing sex differences in spontaneous autonomic fluctuations of resting heart rate using a similarity graph theory approach.","authors":"Lin Sørensen, Elisabet Kvadsheim, Julian Koenig, Julian F Thayer, DeWayne P Williams, Hayley J MacDonald, Ryan Douglas McCardle, Daniel Wollschlaeger, Ole Bernt Fasmer, Berge Osnes","doi":"10.1186/s13293-026-00904-x","DOIUrl":"10.1186/s13293-026-00904-x","url":null,"abstract":"<p><strong>Background: </strong>Autonomic control of the heart is an important indicator of self-regulation and overall mental and physical health. The vagus nerve plays a central role in this regulation, and resting-state heart rate variability (HRV), reflecting fluctuations in inter-beat intervals (IBIs), is the primary noninvasive marker of vagal activity. As males and females differ in aspects of self-regulation, HRV may help elucidate underlying neurobiological differences. However, sex differences in commonly used HRV metrics, such as natural log transformed root mean square of successive RR interval differences (lnRMSSD) and high-frequency HRV (lnHF-HRV) derived from 5-minute recordings, appear smaller in young adults than in other age groups. These metrics capture vagally mediated activity as averaged linear measures and may therefore overlook rapid, spontaneous IBI fluctuations. In the present study, we tested whether a similarity graph theory algorithm could better capture sex differences in nonlinear, rapid IBI variability within 2-5-seconds time windows.</p><p><strong>Methods: </strong>Electrocardiogram (ECG) recordings of 269 young, healthy adults between 18 and 30 years old (M = 21.5, SD = 3.0) were pooled from three different studies. Males accounted for 52.4% of participants, indicating a comparable distribution between sexes. Similarity graph-theory metrics were computed to quantify nonlinear, rapid interbeat interval (IBI) variability using sliding windows of 2-5 s and ≥12 s. In addition, conventional linear and nonlinear heart rate variability metrics, including lnRMSSD and lnHF-HRV, were calculated. Logistic regression models were used to assess the predictive value of graph-theory and HRV metrics for sex, both separately and in combined models for comparison. All models were adjusted for age, body mass index, mean heart rate, and respiratory rate.</p><p><strong>Results: </strong>Males showed higher graph-metric values, indicating lower IBI variability compared with females (odds ratio 2.78; 95% CI 1.32-5.86). Neither lnRMSSD nor lnHF-HRV distinguished sexes alone; however, lnRMSSD became predictive when combined with the graph metric (odds ratio 1.73; 95% CI 1.06-2.81), although this effect was attenuated after controlling for mean heart rate.</p><p><strong>Conclusions: </strong>These findings suggest that nonlinear methods sensitive to rapid spontaneous IBI changes can complement traditional short-term HRV metrics for assessing sex differences in autonomic heart regulation.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761038","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 effects of 17-β-estradiol and bisphenol A on neutrophil function and phenotype - does centrifugation matter?","authors":"Kathrin Fürst, Michael Gruber, Diane Bitzinger, Richard F Kraus","doi":"10.1186/s13293-026-00906-9","DOIUrl":"10.1186/s13293-026-00906-9","url":null,"abstract":"<p><strong>Background: </strong>Neutrophils (polymorphonuclear leukocytes, PMNs) have long been underestimated in the context of autoimmunity. To elucidate their role from a sex-specific perspective, an immunoendocrinological framework offers a compelling investigative approach. We hypothesize that the sex hormone 17-β-estradiol (E2) and the endocrine-disrupting chemical bisphenol A (BPA) modulate PMN functions in a sex- and concentration-dependent manner. In addition, we consider the potential confounding effects of centrifugation protocols employed during PMN isolation.</p><p><strong>Methods: </strong>PMNs from healthy women and men were incubated with different concentrations of E2 (zero; low: 0.01 µM; high: 5µM) and BPA (zero; low: 1.6 µM; high: 16 µM). Migration behavior was assessed using live-cell imaging (n = 6 per concentration). Changes in cell surface expression and oxidative burst were quantified by flow cytometry (n = 12 per concentration).</p><p><strong>Results: </strong>Among samples from females, low doses E2 and BPA significantly reduced chemotactic migration. High substance concentrations led to a significant track length increase. Samples from males showed impaired migration after BPA incubation and increased migration behavior in the presence of E2 in both concentrations. Partially altered antigen expression was seen only in samples from females. Hereby, both concentrations of the tested substances caused reduced CD11b expression. Low dose E2 increased CD66b expression, low dose BPA induced higher LOX-1 expression. At the low concentration level, both substances led to an increase in Phorbol 12-myristate 13 acetate-stimulated oxidative burst. For PMNs from women, this also applied to high dose E2.</p><p><strong>Conclusion: </strong>Different concentrations of the hormone E2 and the endocrine-disrupting chemical BPA modulated neutrophil functions and phenotypes. The effects appeared to be sex-specific, providing a possible explanation for sex-specific immune responses. The data are consistent with the hypothesis that centrifugation impairs PMN functions and showed remaining substance effect despite of centrifugation.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760665","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 efficacy and safety of short-term and de-escalation DAPT strategies after PCI: a network meta-analysis.","authors":"Hao-Yun Lo, Su-Kiat Chua, Jen-Kuang Lee, Donna Shu-Han Lin","doi":"10.1186/s13293-026-00903-y","DOIUrl":"10.1186/s13293-026-00903-y","url":null,"abstract":"<p><strong>Background: </strong>Sex differences in thrombotic and bleeding risks after percutaneous coronary intervention (PCI) are well established, yet it remains uncertain whether the efficacy and safety of modern dual antiplatelet therapy (DAPT) strategies differ between men and women.</p><p><strong>Objectives: </strong>This study aimed to compare sex-specific outcomes of contemporary short-term and de-escalation DAPT strategies to guide individualized post-PCI management.</p><p><strong>Methods: </strong>A network meta-analysis of randomized controlled trials reporting sex-stratified outcomes for alternative DAPT strategies versus standard DAPT was performed. Strategies were categorized as standard DAPT, guided de-escalation, short DAPT followed by aspirin or P2Y12 inhibitor (P2Y12i) monotherapy, de-escalation to clopidogrel, or de-escalation to reduced-dose P2Y12i. The primary outcomes were major adverse cardiovascular events (MACE), bleeding, and net adverse clinical events (NACE).</p><p><strong>Results: </strong>A total of 25 trials including 115,223 men and 38,574 women were analyzed. For MACE, no strategy was superior in men, while de-escalation to clopidogrel showed a favorable trend in women. In men, short DAPT followed by aspirin (risk ratio [RR] 0.44, 95% confidence interval [CI] 0.27-0.73) or P2Y12 inhibitor monotherapy (RR 0.52, 95% CI 0.39-0.70) reduced bleeding, whereas this benefit was not observed in women (P for sex difference = 0.015). De-escalation to clopidogrel provided the lowest bleeding risk and the most favorable NACE profile in women.</p><p><strong>Conclusions: </strong>Sex-based differences exist in the optimal DAPT strategy following PCI, with short DAPT followed by monotherapy robustly reducing bleeding risk in men, while de-escalation to clopidogrel showed the most favorable profile for bleeding and net clinical outcomes in women. However, this finding should be considered hypothesis-generating pending confirmatory evidence, and underscores the need for dedicated prospective trials evaluating sex-specific antiplatelet strategies after PCI.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13235097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760710","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 proteomic response to ischemic stroke.","authors":"Christopher J McLouth, Hunter S Hazelwood, Jacqueline A Frank, Jordan P Harp, David Dornbos, Justin F Fraser, Keith R Pennypacker","doi":"10.1186/s13293-026-00907-8","DOIUrl":"10.1186/s13293-026-00907-8","url":null,"abstract":"<p><strong>Background: </strong>Women often experience greater disability after ischemic stroke than men, but the biological mechanisms underlying these differences remain unclear. Proteomic analysis may identify sex-specific molecular pathways that contribute to stroke rehabilitation and recovery.</p><p><strong>Methods: </strong>We analyzed plasma samples from 141 patients enrolled in the Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC). Expression of 184 inflammatory and cardiometabolic proteins, measured proximal and distal to the clot, was quantified using Olink panels. Associations between protein expression and discharge outcomes - including the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS), and Montreal Cognitive Assessment (MoCA) - were evaluated with models including a sex by protein interaction term, adjusting for clinical and demographic covariates.</p><p><strong>Results: </strong>The median age was 69 years, and 55% were women. After controlling the false discovery rate, systemic TGFBI was expressed at higher levels in men. Multiple proteins demonstrated sex-specific associations with discharge outcomes. For NIHSS, systemic PCOLCE and NT3, as well as intracranial FGF5, NT3, TNFSF14, and TWEAK, were differentially associated by sex, with higher expression generally linked to worse outcomes in women and protective trends in men. For mRS, systemic ICAM3 and TGFBI were associated with higher odds of poor mRS scores in women, while SELL showed a potential protective effect in men. Intracranial CD6 and LAP TGF-β1 also demonstrated sex-specific associations with mRS scores. No sex-specific associations were observed for MoCA.</p><p><strong>Conclusions: </strong>Several sex dependent proteins were associated with post-stroke discharge outcomes. These findings suggest that sex-specific molecular responses could contribute to disparities in post-stroke recovery and highlight the importance of incorporating sex as a biological variable in biomarker studies as well as stratifying clinical trials based on sex.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721699","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 impact of APOE genotype, age, and sex on gut microbiota in a mouse model of Alzheimer's Disease: an exploration of their interactions.","authors":"Xue Mi, Yi-Chi Zhang, Xu-Jun Zhang, Hao-Bing He, Xiao-Chun Chen, Xiao-Man Dai","doi":"10.1186/s13293-026-00905-w","DOIUrl":"10.1186/s13293-026-00905-w","url":null,"abstract":"<p><strong>Background: </strong>As an important interface between the peripheral environment and the central nervous system, the gut microbiota varies greatly between patients or animals with Alzheimer's disease (AD) and their respective non-AD counterparts; however, it remains unexplored whether the apolipoprotein E (APOE) genotype, age, and sex may interactively influence the characteristics of gut microbiota in AD animals.</p><p><strong>Methods: </strong>APOE genotype, age, and sex were enrolled as independent variables, with genotype distinguished into APOE3 and APOE4, age into 3 and 10 months, and sex into female and male. The composition, structure, and potential functions of gut microbiota were systematically analyzed by 16S rRNA gene amplicon sequencing to evaluate the individual and interactive effects of APOE genotype, age and sex.</p><p><strong>Results: </strong>Significant interactions were observed among APOE genotypes, ages, and sexes, with different factor combinations exhibiting distinct effect on microbiotic composition and functional potential. APOE genotype exerted the most significant influence on gut microbiota, followed by age and sex with a relatively minor effect, highlighting the dominant role of host genetic background. Functional prediction analysis indicated that the functional profiles were mainly concentrated in basic metabolic pathways, including the biosynthesis of secondary metabolites and amino acids, and carbon metabolism.</p><p><strong>Conclusion: </strong>APOE genotype, age, and sex are jointly associated with the structure and potential function of the gut microbiota in AD model mice. These findings provide a perspective of multi-factor interaction into the alterations in gut microbiota in AD and offer new microecological evidence for understanding APOE4-related AD susceptibility, as well as a conceptual basis for future stratified microecological intervention studies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721676","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 influences on tumor innervation.","authors":"Sarah M Barclay, Jeffrey Barr, Oduduabasi Isaiah, Mangalam Bajpai, Hailey Bullard, Ethan Neufeld, Craig C Welbon, Payal Ghosh, Destiny S Brockhaus, William C Spanos, Paola D Vermeer","doi":"10.1186/s13293-026-00887-9","DOIUrl":"10.1186/s13293-026-00887-9","url":null,"abstract":"<p><p>Peripheral solid malignancies are infiltrated by nerves. Using syngeneic cell lines, we set out to define whether sex influences tumor innervation in oral cancers and melanoma. Tumors grew significantly slower in females and were significantly more innervated than in males. In oral cancer, tumor-infiltrating nerves connect to a pre-existing neural circuit that enters the brain and impacts behavior. Thus, we evaluated the impact of sex on this circuit and assessed the behavioral consequences. We found no differences in the timing or extent of behavioral declines between oral tumor-bearing males and females. Moreover, in untreated mice, metastasis did not differ by sex. Treatment of oral tumors with cisplatin and radiation slowed tumor growth in male and female mice but significantly increased tumor innervation with females harboring the greatest innervation density. Treated females also harbored significantly increased metastases in their lungs compared to treated males. Treatment improved tumor-associated behavioral changes. While the tumor-brain circuit did not differ between males and females, the activation status of neurons and glia in projection areas significantly increased on the ipsilateral side. This heightened activation was attenuated following cisplatin/radiation treatment. These studies indicate that peripheral malignancies activate neurons and glia in central nervous system (CNS) projection areas, and that standard-of-care therapy attenuates this, which correlates with improved behavior. These findings emphasize that sex influences peripheral tumor-infiltrating nerves and brain function (via the tumor-brain circuit) and suggest that severing or silencing this circuit could improve patient outcomes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653640","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}