Biology of Sex Differences最新文献

{"title":"Sex-biased transcriptomic landscapes in bipolar disorder: integrating neurobiology and clinical heterogeneity through cross-study meta-analysis.","authors":"Omran Davarinejad, Mohammad-Taher Moradi, Arash Safarzadeh, Masumeh Jalalvand, Fatemeh Kazemisafa","doi":"10.1186/s13293-026-00870-4","DOIUrl":"https://doi.org/10.1186/s13293-026-00870-4","url":null,"abstract":"<p><strong>Background: </strong>Bipolar disorder (BD) exhibits significant sex differences in its frequency, symptom presentation, and treatment response, suggesting distinct underlying neurobiological mechanisms. However, transcriptomic studies investigating these sex-specific pathways have been fragmented and underpowered.</p><p><strong>Method: </strong>We conducted the first meta-analysis of post-mortem brain RNA-seq data to delineate sex-related transcriptomic landscapes in BD. We integrated data from four public datasets (GSE80336, GSE80655, GSE202537, GSE42546) from GEO and Array Express, comprising an aggregate of 173 individuals (66 BD cases and 117 controls). After preprocessing and correcting for batch effects, sex-stratified expression analysis was performed using DESeq2. A meta-analysis was conducted with the metafor package to identify differentially expressed genes (DEGs) at an FDR < 0.05. We also performed functional enrichment, protein-protein interaction (PPI) network analysis, hub gene identification, regulatory network reconstruction, and supplementary quantitative analyses of sex-specific interaction effects.</p><p><strong>Results: </strong>Our results reveal striking differences in transcriptomic signatures between men and women with bipolar disorder, with the most pronounced changes occurring in the brain. A meta-analysis across brain regions identified 34 significantly dysregulated genes. In females, upregulated genes were enriched for hormonal signaling (FSHR pathway, G-protein signaling) and transcriptional/epigenetic regulation (GLIS1, neural plasticity). In males, upregulated genes were involved in synaptic calcium signaling (PDLIM5, dendritic spine regulation) and DNA mismatch repair pathways (PMS1). Analysis of the striatum identified 289 differentially expressed genes. The most significantly upregulated genes in females were implicated in immunity and synaptic plasticity, while the male-specific pattern pointed to alterations in basic cellular functions like structure, internal communication, and genetic regulation. A quantitative interaction analysis revealed a negligible correlation (r = -0.122) between disease effect sizes in females and males and identified one gene with opposing, sex-dependent dysregulation (MEF2C).</p><p><strong>Conclusion: </strong>This study provides robust evidence that bipolar disorder engages fundamentally distinct molecular pathways in males and females, underscoring the necessity of integrating sex as a biological variable in psychiatric research and advancing toward personalized therapeutic strategies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highlight on Dr. Rhonda Voskuhl: a pioneer in the exploration of sex differences in the immune response.","authors":"Shannon E Dunn","doi":"10.1186/s13293-026-00910-z","DOIUrl":"https://doi.org/10.1186/s13293-026-00910-z","url":null,"abstract":"","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence predicts sex-specific risk of metabolic dysfunction-associated steatotic liver disease.","authors":"Mohamad Jamalinia, Giovanni Targher, Amedeo Lonardo, Seyed Taghi Heydari, Kamran Bagheri Lankarani","doi":"10.1186/s13293-026-00917-6","DOIUrl":"https://doi.org/10.1186/s13293-026-00917-6","url":null,"abstract":"<p><strong>Background & aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits well-established sex differences across its risk factors, disease progression, and liver-related and extrahepatic outcomes. We trained sex-specific machine learning (ML) algorithms using routine clinical data to evaluate sex-specific learning patterns and diagnostic performance.</p><p><strong>Methods: </strong>In this cross-sectional study conducted at a cardiology referral center, 446 adults were enrolled. Participants were divided into training (127 men, 185 women) and test sets (55 men, 79 women). Eight ML classifiers were trained on the overall dataset and separately for men and women to predict MASLD presence and steatosis severity (no/mild/moderate-to-severe) as assessed by ultrasonography. Hyperparameters were tuned using grid search cross-validation, and model performance was evaluated on an unseen test set.</p><p><strong>Results: </strong>The prevalence of MASLD was 63.6% among participants; 41.2% had mild, and 22.4% had moderate-to-severe steatosis. Compared to models trained on the overall dataset, sex-specific modeling improved diagnostic performance in men but remained suboptimal in women. For MASLD presence, top-performing models achieved AUC/F1 scores of 0.769/0.856 overall, 0.793/0.897 in men, and 0.681/0.794 in women. For steatosis severity, respective AUC/F1 scores were 0.761/0.671 overall, 0.723/0.608 in men, and 0.718/0.571 in women. Sensitivity analyses using stratified cross-validation confirmed the performance gap between men and women. Threshold analyses showed acceptable rule-in and rule-out performance in men but suboptimal performance in women. Feature-importance rankings differed substantially between sexes, indicating distinct sex-specific learning patterns.</p><p><strong>Conclusions: </strong>Artificial intelligence-based algorithms identify sex-specific learning patterns in MASLD steatosis risk prediction. Routine clinical variables appear more informative for men, while showing weaker algorithmic performance in women. This finding suggests that failure to train MASLD risk algorithms with sex-specific risk factors may increase the risk of misclassification in women. Therefore, achieving more equitable and clinically reliable models will require integrating women-specific risk factors and adopting sex-stratified data processing strategies within MASLD prediction frameworks to reduce diagnostic inequities and support more personalized care.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproductive history differentially shapes the neural response of middle-aged hAPOEɛ4 female rats to estradiol therapy after a metabolic challenge.","authors":"Jennifer E Richard, Ahmad Mohammad, Stephanie E Lieblich, Kimberly A Go, Soda Wang, Rebecca K Rechlin, Tallinn F L Splinter, George E Barreto, Liisa A M Galea","doi":"10.1186/s13293-026-00911-y","DOIUrl":"https://doi.org/10.1186/s13293-026-00911-y","url":null,"abstract":"<p><strong>Background: </strong>Advancing age, the APOEɛ4 allele, and female sex are the top nonmodifiable risk factors for Alzheimer's disease (AD). Female-specific experiences, such as parity and hormone therapy (HT) affect aging biomarkers such as metabolism and immune signaling, and may affect AD risk. Estradiol (E2), a component of many HTs, affects cognition and brain health in aging females although studies suggest the effects can vary depending on parity, genotype, and metabolic status which may account for some of the inconsistencies in the literature. We hypothesized that prior parity influences brain and metabolic health, including response to E2, depending on APOE genotype.</p><p><strong>Methods: </strong>Middle-aged female (10 month) wildtype (WT) or humanized (h) APOEɛ4 expressing rats, with different reproductive experience (nulliparous or primiparous) were fed a Western (WD) or standard diet (SD) for 2 months. In the second month, rats were given E2 or vehicle (oil) injections daily. Fear associative learning, plasma metabolic hormones, hippocampal inflammatory cytokine expression, and neuroplasticity (neurogenesis, synaptic protein) were assessed.</p><p><strong>Results: </strong>Females fed a WD gained weight and displayed metabolic dysregulation, regardless of genotype. E2 treatment reduced WD-induced weight gain and reduced metabolic hormones, with stronger effects in WT rats. E2 treatment increased dorsal hippocampal inflammatory cytokine expression selectively in primiparous hAPOEɛ4 females fed a WD. Previous parity increased neurogenesis and reduced certain cytokine expression in the hippocampus of middle-aged WT rats under a SD. Both E2 treatment and previous parity decreased dorsal neurogenesis in hippocampus of hAPOEɛ4 rats. In hAPOEɛ4 females, higher weight was associated with reduced contextual fear memory, an effect driven by primiparous females. In the cued fear conditioning task, hAPOEɛ4 females displayed better cued fear memory than WT, however, WD exposure reduced cued fear memory only in this group. Together, this indicates that diet and weight gain may be more detrimental to associative memory in hAPOEɛ4 females and that E2 treatment has more favourable outcomes in WT rats.</p><p><strong>Conclusions: </strong>Previous parity alters how females respond to E2 and metabolic stress in midlife. Primiparous hAPOEɛ4 females were especially vulnerable to the effects of WD and E2, exhibiting more inflammation, impaired memory, and reduced weight-loss. These findings highlight the importance of considering parity and genotype when evaluating midlife metabolic and cognitive risk.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"https://doi.org/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":5.1,"publicationDate":"2026-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":5.1,"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":"https://doi.org/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":5.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":5.1,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":5.1,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":5.1,"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}