Biology of Sex Differences最新文献

{"title":"Sex differences in cardiac recovery and ventricular gene expression in a rat model of donation after circulatory death.","authors":"Anja Helmer, Alexia Clavier, Maria Arnold, Adrian Segiser, Heidi E L Lischer, Selianne Graf, Mojgan Masoodi, Georgia Beer, Rahel Ottersberg, Manuel Egle, Matthias Siepe, Sarah Longnus","doi":"10.1186/s13293-026-00915-8","DOIUrl":"10.1186/s13293-026-00915-8","url":null,"abstract":"<p><strong>Background: </strong>Heart donation after circulatory death (DCD) is a promising strategy to increase graft supply. However, in contrast to conventional heart transplantation, in which organs are retrieved from heart-beating donors, DCD hearts are subjected to damaging conditions before and during functional, warm in-situ ischemia in the donor, leading to ischemia-reperfusion injury (IRI). Although sex differences have been identified in other contexts of cardiac IRI, such as myocardial infarction, they remain underexplored in DCD. Therefore, we aimed to investigate whether sex differences induce changes in the expression of genes in response to cardiac DCD conditions, including IRI, which may contribute to sexual dimorphism in graft quality.</p><p><strong>Methods: </strong>102 animals were included in this study. Male, female, and ovariectomized (OVX) Wistar rats underwent simulated DCD with no or 22 min of functional, warm in-situ ischemia, followed by oxygenated reperfusion with left-ventricular loading. Functional recovery was assessed and left-ventricular tissue was used for RNA-sequencing.</p><p><strong>Results: </strong>Recovery of left ventricular function was decreased by functional, warm in-situ ischemia, but significantly better in females than in males, with OVX resembling the males. Reperfusion induced inflammatory, stress-response and metabolic-related pathways in all groups. Expression of 110 genes correlated with cardiac recovery, many of which were more abundant in females compared to males, consistent with a role in improved post-ischemic ventricular function. Among these genes, Igfbp3, Fam78b, and Galnt10 were differentially expressed in females compared to males and OVX, suggesting an influence of female sex hormones.</p><p><strong>Conclusions: </strong>Compared to male hearts, cardiac recovery is significantly higher in female hearts after exposure to DCD conditions and is accompanied by an increased expression of genes related to quality control programs that positively correlate with ventricular function. Significantly higher expression of genes related to energy metabolism, including fatty acid metabolism, and inflammatory pathways was revealed in males compared to females and is associated with decreased recovery. This study suggests potential new therapeutic targets for optimizing cardiac DCD graft quality, and highlights the importance of underlying sex and sex-hormone differences, e.g. in inflammatory pathways and metabolic adaptations, that should be taken into consideration for the implementation of sex-specific precision therapies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004418","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 between pregnancy zone protein and acute coronary syndrome: a case-control study.","authors":"Xinxin Shen, Xiaobin Guo, Ting Yang, Kaifang Yang, Weilin Wang, Huimin Chen, Fengling Lai, Mingjun Zhang, Yan Zheng, Guohai Su, Keqing Hu, Rong Huang","doi":"10.1186/s13293-026-00926-5","DOIUrl":"10.1186/s13293-026-00926-5","url":null,"abstract":"<p><strong>Background: </strong>Pregnancy zone protein (PZP) is a highly glycosylated macromolecular protein involved in energy metabolism, fibrinolysis, and immunomodulation. However, its association with acute coronary syndrome (ACS), particularly regarding sex differences, remains to be fully elucidated.</p><p><strong>Methods: </strong>ACS patients were enrolled from the Department of Cardiology, and control subjects were recruited from the Health Examination Department. Plasma levels of PZP were quantified using a sandwich enzyme-linked immunosorbent assay (ELISA). Spearman's correlation was used to analyze the association between PZP levels and clinical variables. The association of PZP with ACS was assessed using logistic regression models, with PZP levels analyzed as a continuous variable, and subsequently categorized into binary and quartile groupings. Potential confounding variables were selected based on the disjunctive cause criterion and were adjusted for in the logistic regression models.</p><p><strong>Results: </strong>In this study, we enrolled 1170 participants, comprising 721 men and 449 women. Plasma PZP exhibited marked sexual dimorphism, with concentrations much higher in women than in men (median [IQR]: 3.46[1.87, 5.88] vs. 0.26[0.10, 0.52] µg/mL; P < 0.01). Among men, PZP levels were significantly elevated in ACS patients compared to controls (median [IQR]: 0.29[0.12, 0.55] vs. 0.15[0.06, 0.32] µg/mL; P < 0.01), whereas no difference was observed in women (median [IQR]: 3.45[1.82, 5.99] vs. 3.48[2.26, 4.89] µg/mL; P = 0.95). Correlation analyses revealed distinct sex-specific patterns: in men, PZP correlated positively with age and inversely with estimated glomerular filtration rate (eGFR), whereas in women, only a weak positive correlation with high-density lipoprotein cholesterol (HDL-C) was observed. In multivariable logistic regression, higher PZP was independently associated with ACS in men across all modeling strategies-continuous (fully adjusted OR 5.90, 95% CI 1.59-24.98; P = 0.011), dichotomized using the Youden-derived cutoff (> 0.25 µg/mL; OR 1.87, 95% CI 1.02-3.50; P = 0.045), and quartile-based (top vs. bottom quartile; OR 4.79, 95% CI 1.74-15.26; P = 0.004)-but no significant association was found in women (fully adjusted continuous OR 1.06, 95% CI 0.86-1.31; P = 0.589).</p><p><strong>Conclusions: </strong>This study establishes that circulating PZP exhibits extreme sexual dimorphism and demonstrates its male-specific association with ACS through absolute quantification. Our findings highlight the necessity of sex-stratified analysis in cardiovascular biomarker research. These findings warrant prospective validation to determine whether PZP has any role in sex-stratified cardiovascular risk assessment, as well as future studies to clarify its temporal dynamics and sex-specific mechanisms.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004410","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":"Gene regulatory network analysis identifies dysregulation of hypoxia pathways as contributing to glioblastoma treatment resistance in females.","authors":"Tomisin Adebari, Viola Fanfani, Marouen Ben Guebila, Derrick DeConti, Katherine Hoff Shutta, Camila M Lopes-Ramos, Lauren Hsu, Dawn L DeMeo, John Quackenbush, Tara Eicher","doi":"10.1186/s13293-026-00927-4","DOIUrl":"10.1186/s13293-026-00927-4","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma or GBM (IDH wild-type) is an aggressive brain tumor that is notoriously resistant to treatment, with an average survival time of 17 months. While the overall outcome is poor for both males and females, sex differences in GBM incidence and outcome suggest sex-specific biological mechanisms underlie tumorigenesis. In contrast, low-grade glioma (LGG) is a less aggressive brain tumor that tends to have a better prognosis and a longer survival time.</p><p><strong>Methods: </strong>To understand mechanisms contributing to treatment resistance in GBM in both males and females, we inferred gene regulatory networks (GRNs) for males and females with LGG and GBM using RNA-seq data from The Cancer Genome Atlas (TCGA). We analyzed these to identify both sex-specific and sex-stratified gene regulation in GBM. We then validated these results on a separate cohort, the Repository of Molecular BRAin Neoplasia DaTa (REMBRANDT).</p><p><strong>Results: </strong>We found sex-specific differential targeting of several pathways, including hypoxia and related pathways (carbohydrate metabolism, innate immune processes, and extracellular matrix pathways) known to be dysregulated in hypoxic conditions, in GBM when compared against LGG. After further evaluating the co-regulation of sex-specific pathways in GBM, we found that females exhibited a greater degree of co-regulation between hypoxia and hypoxia-associated transcriptional programs with the aforementioned downstream pathways than did males.</p><p><strong>Conclusions: </strong>Our results suggest that dysregulation of hypoxia-related pathways in GBM plays a female-specific role in resistance to treatment and overall outcomes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986410","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":"Association of testosterone and sex hormone-binding globulin with chronic liver disease outcomes across sex and menopausal status.","authors":"Luna Liu, Wenhui Liu, Yingzhou Shi, Xiaoran Cha, Panpan Yin, Qingbo Guan, Xiude Fan, Mo Wang","doi":"10.1186/s13293-026-00923-8","DOIUrl":"10.1186/s13293-026-00923-8","url":null,"abstract":"<p><strong>Background & aims: </strong>The influence of sex hormones on chronic liver disease (CLD) progression remains unclear, despite sex-related differences in disease susceptibility and outcomes. This study aimed to investigate the associations of total testosterone (TT) and sex hormone-binding globulin (SHBG) levels with CLD-related outcomes across sex and menopausal status.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using UK Biobank data. Serum TT and SHBG levels were measured at baseline. Participants were followed for incident liver fibrosis and cirrhosis, hepatocellular carcinoma (HCC), and liver-related death. Cumulative risk curve, restricted cubic spline, and multivariable Cox proportional hazards models were used to assess TT and SHBG associations with outcomes in males, premenopausal females, and postmenopausal females.</p><p><strong>Results: </strong>A total of 155,997 males, 79,637 postmenopausal females, and 28,174 premenopausal females were included, with a median follow-up of 13.53 years. Cumulative risk curve showed that males had the highest risk of CLD-related outcomes (P < 0.001). Males in the highest quartile of SHBG had hazard ratios (HRs) of 3.58 for liver fibrosis and cirrhosis, 4.31 for HCC, and 5.18 for liver-related death compared to the lowest quartile. In the highest TT quartile, the HRs were 2.17 for liver fibrosis and cirrhosis, 2.22 for HCC, and 2.50 for liver-related death. In postmenopausal females, only SHBG levels were positively associated with outcomes, though weaker than males. No significant associations were observed in premenopausal females.</p><p><strong>Conclusions: </strong>Elevated TT and SHBG levels are associated with higher risks of CLD-related outcomes, particularly in males. Further studies are needed to clarify the causal roles and mechanisms.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986415","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 modifiable risk factors of dementia and their associations with cognition.","authors":"Megan C Fitzhugh, Judy Pa","doi":"10.1186/s13293-026-00908-7","DOIUrl":"10.1186/s13293-026-00908-7","url":null,"abstract":"<p><strong>Background: </strong>Women have a greater lifetime risk of developing dementia. Despite clear sex differences, studies investigating modifiable dementia risk factors often overlook differences between sexes and age. This study examined sex and age differences in the prevalence of modifiable dementia risk factors and their associations with cognition.</p><p><strong>Methods: </strong>Participants were from the Health and Retirement Study, a nationally representative cohort study. Thirteen risk factors were examined, including education, hearing loss, cholesterol, depression, physical inactivity, diabetes, smoking, hypertension, obesity, excessive alcohol use, social isolation, poor vision, and poor sleep. A global cognitive summary score was also examined. Chi-square and t-tests examined sex and age differences in prevalence; linear regression examined interactions between sex, age, and risk factors on cognition.</p><p><strong>Results: </strong>This study included 17,182 participants with a mean age of 69.2 ± 10.6 years, 59.2% of which were women. Ten out of 13 risk factors had sex differences in prevalence. Women had higher prevalence of elevated cholesterol, depression, physical inactivity, smoking, poor vision, and poor sleep. Women also had fewer years of education. Men had a higher prevalence of hearing loss, diabetes, and excessive alcohol use. Hearing loss, diabetes, and hypertension were associated with greater effects on cognitive performance in woman than men. BMI was negatively associated with cognitive performance in women compared to men in their 50s and 60s, but not at older ages. Education and cholesterol had stronger, positive associations with cognitive performance in women compared to men.</p><p><strong>Conclusions: </strong>These data suggest that women's greater risk of dementia may be due to a higher prevalence of multiple risk factors and stronger cognitive effects of risk factors. Results may inform future personalized prevention strategies for dementia risk reduction, particularly in women.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13188715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969874","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":"Integrated multi-omics analysis reveals a gut microbiota-tryptophan metabolism axis contributes to sex differences in a β-aminopropionitrile-induced aortic dissection mouse model.","authors":"Shuai Cheng, Xinyu Hao, Shirui Liu, Linfeng Zhang, Shuai Zhang, Yutian Chen, Lei Wang, Shijie Xin, Zhen Li, Zhaohui Hua, Hui Cao","doi":"10.1186/s13293-026-00925-6","DOIUrl":"10.1186/s13293-026-00925-6","url":null,"abstract":"<p><strong>Background: </strong>Sex differences in aortic dissection (AD) have been consistently reported in epidemiological studies and experimental mouse models, with males showing markedly higher susceptibility. However, the molecular basis underlying these sex-specific differences remains insufficiently understood.</p><p><strong>Methods: </strong>Three-week-old male and female C57BL/6J mice were administered 0.4% β-aminopropionitrile (BAPN) in drinking water for 28 d to induce AD. After the induction period, fecal samples, serum, and aortic tissues were collected from all surviving animals. Integrated analyses included strand-specific transcriptomic sequencing of aortic tissues, untargeted serum metabolomics, and full-length 16 S rRNA sequencing of fecal samples to characterize sex-related differences across transcriptomic, metabolic, and microbiome layers. Inter-omics correlations were further assessed using bioinformatic approaches. Furthermore, in vivo experiments were conducted to validate the impact of key metabolites on the progression of AD.</p><p><strong>Results: </strong>Female mice exhibited significantly lower susceptibility to BAPN-induced AD, including reduced rates of aortic rupture, lower incidence of AD or aneurysm (AAD), and attenuated aortic dilation. Transcriptomic analysis revealed that female non-dissected mice (FeNonAD) displayed diminished induction of inflammation-related genes and lower predicted immune cell infiltration. Metabolomic profiling revealed significant elevations of tryptophan-indole pathway metabolites-such as indolepyruvate, indole-3-acetic acid, and indolepropionic acid-in both FeNonAD and AAD groups. Microbiome analysis further revealed a higher relative abundance of tryptophan-metabolizing taxa, particularly key Clostridium species, in the intestinal tract of FeNonAD mice, accompanied by significant upregulation of key functional genes (tyrB and aspC) associated with indolepyruvate synthesis. Weighted gene co-expression network analysis (WGCNA)-based integration identified strong negative correlations between indolepyruvate and indole-3-acetic acid sodium salt levels and aortic gene modules linked to immune-inflammatory activation. Further in vivo experiments demonstrated that treatment with indolepyruvate delayed AD progression in male mice.</p><p><strong>Conclusion: </strong>This study highlights a central \"gut microbiota-tryptophan metabolism-aortic inflammation\" axis that contributes to sexual dimorphism in BAPN-induced AD. These findings provide new molecular insights into sex-specific disease mechanisms and offer a conceptual basis for developing sex-tailored diagnostic and therapeutic strategies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969850","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":"Media matters: phenol red and fetal bovine serum estrogen in traditional cell culture media influence human mesenchymal stromal cell (hMSC) processes and differentiation in a sex-biased manner.","authors":"John C Bradford, Jennifer L Robinson","doi":"10.1186/s13293-026-00921-w","DOIUrl":"10.1186/s13293-026-00921-w","url":null,"abstract":"<p><p>Estrogens are global regulators of cellular signaling pathways, impacting fundamental processes and phenotypes that are essential for tissue remodeling and homeostasis. Traditional cell culture media contains estrogen-mimetic compounds, including phenol red and endogenous estrogen in fetal bovine serum (FBS). However, the potential of these compounds to bias in vitro studies, particularly when considering sex as a biological variable, remains unclear. This gap in understanding critically impacts the culture of human mesenchymal stromal cells (hMSCs), whose basic functions and differentiation potential, central to cell therapy and tissue engineering, are sensitive to perturbations in the culture conditions. Despite this, the effect of estrogens from cell culture media on male and female hMSCs is not currently considered in cell processing for clinical trials. As such, a baseline understanding of these estrogen-mimetic media influences on hMSCs is critical for clinical efficacy and adequate study design in research. To this end, we investigated the effects of phenol red and fetal bovine serum on the proliferation, metabolism, senescence, and differentiation capacity of male and female hMSCs. Phenol red, FBS, donor sex, and 17β-estradiol (E2) supplementation all had significant impacts on hMSC health and differentiation potential in culture. Notably, dosing with estrogen at the levels found in FBS did not recover most of the hMSC metrics tested. The notable outcomes that were significantly impacted by sex for the overall analysis include proliferation, metabolism, senescence, osteogenic differentiation, adipogenic differentiation, and gene expression for Col1a1, ESR1, Col10a1, RUNX2, FABP4, and PPARγ. Donor variability was a main driver in all the outcomes tested, highlighting the need for personalized medicine in research investigating cellular response to hormone signaling. Overall, these findings reveal the sex-biased effects of estrogen and estrogen-mimetic compounds in traditional culture media, underscoring a current gap in considering sex as a biological variable in cell therapy and tissue engineering research and manufacturing.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969867","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":"Developmental and dynamic systems: insights for sex/gender research.","authors":"Giordana Grossi, Annie Duchesne, Donna L Maney","doi":"10.1186/s13293-026-00920-x","DOIUrl":"10.1186/s13293-026-00920-x","url":null,"abstract":"<p><p>Recent work incorporating gender into sex differences research has complicated the interpretation of both physiological and behavioral differences between women and men, which are traditionally interpreted as driven by \"biological\" sex-related variables. Alternative conceptualizations have been proposed to capture the complex relationship between sex and gender, such as sex/gender entanglement. Blurring the boundaries between gender and sex, the organism and its environments, this perspective has created a need for theoretical and methodological approaches that can be used to investigate the emergence of structures and behaviors in complex systems. Here, we review the foundational concepts of developmental and dynamic systems theories, which can serve as frameworks within which to investigate the emergence of complex phenomena. We then provide examples of empirical research programs that demonstrate the benefit of these frameworks in the context of sex/gender research.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147959538","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 relationships between stress coping and avoidance behavior in adult mice.","authors":"Kailyn M Price, Abigail M Polter","doi":"10.1186/s13293-026-00918-5","DOIUrl":"10.1186/s13293-026-00918-5","url":null,"abstract":"<p><p>While the experience of stress is ubiquitous, the risk of developing stress-linked conditions such as anxiety and depression is related to maladaptive stress responses. In order to probe the relationship between stress coping, sex, and stress-linked behavioral outcomes, we exposed male and female mice to subchronic variable stress (SCVS) and measured the correlation between coping during the tail suspension stressors (TSS) of SCVS and avoidance behavior in the EPM. We found that females engage in more active coping, and there were no sex differences in avoidance or locomotor behavior in the EPM after stress. However, we found that greater active coping predicted greater avoidance in females, but less avoidance in males. The results demonstrate that coping strategies are dynamic across time in males and females, but the relationships between avoidance and coping strategy dynamics are sex-biased.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13348443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925986","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":"Importance of integrating biological sex and age analyses in health research.","authors":"DeLisa Fairweather, Georgios Kararigas","doi":"10.1186/s13293-026-00900-1","DOIUrl":"10.1186/s13293-026-00900-1","url":null,"abstract":"<p><p>Research findings in human, animal and cell populations may be influenced by biological sex and age. The traditional statistical approach to sex and/or age differences that are discovered in research data is to consider them as confounders that interfere with the ability to make accurate estimations and thus need to be controlled for. This article provides examples of how combining sexes or controlling for sex and/or age may lead to inaccurate findings and overlook important insights. Rather than treating these variables as confounding factors, they should be viewed as variables of importance to the research question. We contend that data should be analyzed according to sex/age as the primary analysis, while controlling for sex and age should be conducted as a secondary analysis. This topic is increasingly important as data are made publicly available and deep learning models/artificial intelligence are used to analyze large volumes of data. Mechanistic insights will continue to be lost if prompt action is not taken to report data according to sex and age and to analyze data by sex and age in health research.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13162372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873059","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}