Biology of Sex Differences最新文献

{"title":"Sex-stratified insights into the genetics of brain volumes in late adulthood.","authors":"Édith Breton, Elleke Tissink, Gloria Matte Bon, Dennis van der Meer, Ole A Andreassen, Tobias Kaufmann","doi":"10.1186/s13293-026-00943-4","DOIUrl":"10.1186/s13293-026-00943-4","url":null,"abstract":"<p><strong>Background: </strong>The prevalence, timing and disease course of mental and neurological disorders vary according to sex, yet the neurogenetic mechanisms underlying sex differences in brain disorders remain poorly understood. While sex chromosomes and hormones contribute to sex differences in brain biology, previous studies suggest a role for autosomal genetic variation as well.</p><p><strong>Methods: </strong>We investigated autosomal genetic associations with brain volumes in 15,740 females and 15,740 males from the UK Biobank, matched for age and scan site, using sex-stratified genome-wide association analyses. We applied a multivariate genome-wide approach (MOSTest) across 257 brain regions and complemented these analyses with region-specific univariate genome-wide association studies.</p><p><strong>Results: </strong>Heritability estimates and genetic correlations were highly similar between females and males in late adulthood, indicating largely shared genetic influences on brain volumes. Many loci reaching genome-wide significance in one sex also showed signal in the other. Gene mapping in these loci yielded a greater total number of brain-volumes associated genes in females than in males. Variability in the number of mapped genes was particularly pronounced in limbic regions such as the insula, cingulate cortex, hippocampus and amygdala.</p><p><strong>Conclusion: </strong>Overall, our findings contribute to a better understanding of autosomal genetic influences on brain volumes in males and females and may inform future studies examining sex variability in neurobiological mechanisms relevant to brain disorders.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444312","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":"Dietary pine pollen induces masculinization in Nile tilapia (Oreochromis niloticus, L. 1758) by modulating sex-biased gene expression and steroid hormone profiles.","authors":"Ivan Abaho, Clifford L W Jones, Peter Akoll, Charles Masembe","doi":"10.1186/s13293-026-00950-5","DOIUrl":"10.1186/s13293-026-00950-5","url":null,"abstract":"<p><strong>Background: </strong>The health and environmental risks associated with using 17-methyltestosterone hormone (MT) to produce all-male tilapia stocks limit the sustainability of aquaculture. As such, plant-based products with the potential to induce masculinisation in tilapia are gaining considerable attention as potentially safe, nature-based alternatives. However, the underlying mechanism for sex change induction by plant products remains unknown. The present study used pine pollen (PP) to study the processes modulating female-to-male sex change in three-day-old all-female Nile tilapia (Oreochromis niloticus).</p><p><strong>Methods: </strong>Experimental fish were fed either a basal diet supplemented with 1,280 mg PP kg^- 1 from 3 to 30 days post-hatch (dph), or the same basal diet incorporated with 60 mg MT kg^- 1 (MT treatment), or the basal diet only (CT treatment. After 30 dph, fish in all treatments were fed only a basal diet up to 120 dph.</p><p><strong>Results: </strong>Histological observations showed that female-to-male sex change occurred between 21 and 45 dph in MT and PP treatments. During this period, gonadal tissue in PP-treated fish progressively shifted from undifferentiated germ cells toward testes dominated by spermatogonia and spermatocytes. In contrast, MT treatment accelerated spermatogenic progression, with gonads exhibiting advanced germ cells, including spermatids and spermatozoa, reflecting complete masculinisation. Conversely, fish in the CT group underwent normal ovarian differentiation between 21 and 30 dph, characterised by ovarian cavity formation and oocyte-like germ cells. These gonadal histological changes were closely related to temporal changes in sex-biased gene expression and steroid hormone profiles. The PP and MT treatments significantly up-regulated male sex gene expression (dmrt1 and amh) and down-regulated female transcripts (cyp19a1a and foxl2), whereas an opposite pattern was observed in the CT group. Correspondingly, sex steroid concentrations (testosterone and 11-ketotestosterone) were also significantly elevated in both PP- and MT-treated fish, consistent with higher proportions of male individuals (PP: 77.8 ± 2.9% and MT: 97.8 ± 1.1%), unlike the CT group, where fish remained all-female with significantly higher 17β-estradiol levels.</p><p><strong>Conclusion: </strong>These findings imply that PP induces female-to-male sex change in Nile tilapia by disrupting the expression of sex-biased genes and, consequently, the androgen-to-estrogen balance. However, further studies are required to enhance the androgenic potency of PP.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410189","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 MASLD-related atherosclerosis: plaque phenotype, vascular dysfunction, and cardiovascular outcomes.","authors":"Mohamad Jamalinia, Ralf Weiskirchen, Amedeo Lonardo","doi":"10.1186/s13293-026-00952-3","DOIUrl":"10.1186/s13293-026-00952-3","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Emerging evidence suggests that the vascular manifestations of MASLD differ substantially between men and women. We therefore hypothesized that the mechanisms, plaque phenotypes, and clinical implications of MASLD-related ASCVD are sex-specific.</p><p><strong>Methods and results: </strong>In this narrative review, we searched PubMed/MEDLINE for studies published up to April 2026 and synthesized current evidence regarding sex differences in MASLD-related atherosclerosis. Available data support a sex-specific vascular paradigm in MASLD. In men, MASLD is more strongly associated with calcified and obstructive coronary atherosclerosis. In contrast, women with MASLD more frequently exhibit non-calcified atherosclerotic phenotypes and functional vascular abnormalities (e.g., endothelial dysfunction, arterial stiffness, and coronary microvascular dysfunction). Importantly, despite lower coronary artery calcium (CAC) burden, women with MASLD experience a disproportionately greater risk of adverse cardiovascular events. Therefore, calcification-centered assessment may inadequately capture ASCVD risk in women with MASLD by failing to identify non-calcified plaque and functional vascular abnormalities. These sex differences are likely mediated by interacting pathobiological and socio-cultural factors, including sex hormones and menopausal transition, adipose tissue distribution, immune-metabolic and inflammatory profiles, genetic susceptibility, and gender influences.</p><p><strong>Conclusion: </strong>MASLD is associated with distinct sex-specific cardiovascular phenotypes that have important clinical implications for ASCVD risk assessment and prevention. Women with MASLD may develop clinically significant ASCVD despite lower CAC burden, supporting a sex- and menopause-aware approach to cardiovascular evaluation. In selected high-risk women, complementary use of multimodality imaging beyond CAC may improve risk stratification and facilitate earlier detection of clinically relevant cardiovascular disease.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403460","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 sleep architecture and nocturnal oxygenation across obstructive sleep apnea severity: an observational hospital-based study.","authors":"Meina Wu, Pei Xue, Jinzhu Yan, Christian Benedict","doi":"10.1186/s13293-026-00951-4","DOIUrl":"10.1186/s13293-026-00951-4","url":null,"abstract":"<p><strong>Background: </strong>Sex differences in obstructive sleep apnea (OSA) may extend beyond the apnea-hypopnea index (AHI), the standard measure of OSA severity, and involve differences in sleep architecture and nocturnal oxygenation. We compared these characteristics between women and men across OSA severity categories in a large Chinese clinical cohort.</p><p><strong>Methods: </strong>This single-center, hospital-based observational study included adults referred for overnight polysomnography at a sleep center in Fujian, China. OSA severity was classified as mild, moderate, or severe according to AHI. Outcomes included total sleep time (TST), sleep stages, sleep fragmentation, nocturnal oxygenation, respiratory event composition, and the relative distribution of oxygen desaturation events between rapid eye movement (REM) and non-REM sleep. Associations between sex, OSA severity, and these outcomes were examined using adjusted generalized linear models.</p><p><strong>Results: </strong>Among 1,632 patients (mean age 57 years; 41.4% women), women exhibited longer TST, a lower proportion of stage N1 sleep, a higher proportion of stage N3 sleep, and lower sleep fragmentation than men, irrespective of OSA severity (all p < .001). Men exhibited a higher proportion of REM sleep than women only in mild OSA (+ 1.46 percentage points, p = .009). Women showed a greater predominance of hypopneas than men in moderate and severe OSA (p = .02 and p < .001, respectively). Women also exhibited lower nadir oxygen saturation (SpO2) values than men across OSA severity categories (p = .001). In addition, women demonstrated a greater predominance of REM-related oxygen desaturation events than men in both moderate and severe OSA (both p < .001).</p><p><strong>Conclusions: </strong>Women and men with similar OSA severity exhibited distinct patterns of sleep architecture, respiratory event composition, and nocturnal oxygenation. These findings suggest that characteristics beyond AHI may provide additional information regarding the physiological expression of OSA, although their clinical relevance remains to be determined.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395650","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 electrophysiological and behavioral responses to nitrous oxide in a murine model of neuropathic pain.","authors":"Gemma González-Hernández, Sonia Torres-Sanchez, Daniel Sanchez-Morillo, Tomi Rantamäki, Esther Berrocoso","doi":"10.1186/s13293-026-00945-2","DOIUrl":"10.1186/s13293-026-00945-2","url":null,"abstract":"<p><p>Chronic pain-depression comorbidity is characterized by sensory hypersensitivity and emotional dysregulation, and has been linked to alterations in prefrontal network connectivity. It represents a major therapeutic challenge due to its pronounced sex differences in symptom manifestation and increased treatment resistance. Nitrous oxide (N₂O), an inhalational anesthetic traditionally used for its analgesic properties, has recently emerged as a potential rapid-acting antidepressant, with evidence suggesting both rapid and sustained antidepressant effects. Here, we evaluated the behavioral and electrophysiological effects of N₂O (50%, 1 h) in adult male and female mice subjected to the chronic constriction injury (CCI) model of neuropathic pain, assessing its potential to simultaneously target nociceptive and affective symptoms, as well as locomotor behavior. N₂O reduced locomotor activity in both sexes, with longer-lasting effects in males. EEG recordings revealed decreased low-frequency spectral power in both sham and CCI animals, with more widespread effects in females. In the acetone test, N₂O produced analgesia in CCI males but no significant effect in females, while stimulus application increased oscillatory EEG activity across groups and sexes. Notably, CCI females showed an attenuated electrophysiological response compared with Sham-Air controls. In sham animals, N₂O reduced post-stimulus power, whereas in CCI mice it restored prefrontal EEG activity, enhancing the electrophysiological responses in both sexes. In the tail suspension test, only CCI males exhibited a prodepressive phenotype, while no antidepressant-like effects were observed in either sex 24 h post-treatment. These findings demonstrate sex-specific behavioral and neurophysiological responses to N₂O, highlighting the importance of incorporating sex as a biological variable in NMDA receptor-targeted interventions.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403396","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 male default prevails in biomedical research: sex inclusion in Nature (2025).","authors":"Ashlyn Swift-Gallant, Liisa A M Galea, Lindsay S Cahill","doi":"10.1186/s13293-026-00947-0","DOIUrl":"10.1186/s13293-026-00947-0","url":null,"abstract":"<p><p>Despite longstanding recognition of sex as a biological variable, its integration into biomedical research remains inconsistent. Numerous publishers have introduced policies to improve reporting and inclusion of sex and gender, including Nature, which requires authors to complete a Life Science Reporting Summary documenting sex inclusion. Here, we evaluated the effectiveness of these policies by examining sex inclusion and reporting practices in all original research articles involving humans, vertebrates, or cell lines published in Nature in 2025 (N = 513). Nearly two-thirds of articles included both sexes (62.7%); however, inclusion was often nominal. Of these articles reporting inclusion of both sexes, 33% did not maintain inclusion across experiments, used markedly unbalanced sex ratios (≥ 2:1), or alternated between male- and female-only experiments. Another 45.5% of these articles reporting inclusion of both sexes did not report sample size by sex, so it cannot be ascertained whether sex inclusion was maintained across experiments or balanced by sex. Single-sex studies accounted for approximately one-fifth of articles. While male-only and female-only studies occurred at similar overall rates, male-only studies were more than four times more likely to address conditions affecting both sexes while female-only studies were more likely to address sex-specific conditions (e.g., ovarian cancer). Notably, the policies aimed at improving reporting and inclusion also did not increase analysis by sex; only 7% of articles explicitly analyzed sex as a discovery variable for at least some analyses. These findings suggest that transparency-focused reporting summaries alone are insufficient to ensure sex inclusion and/or meaningful analytical integration of sex (i.e., direct comparison of sexes, rather than using sex as a covariate). As a leading biomedical journal, Nature plays a central role in shaping research norms; without stronger editorial expectations, reporting requirements risk reinforcing male-default assumptions rather than advancing rigor and generalizability.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395684","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":"Correction: Circulating nitric oxide pathway metabolites in heart failure with preserved ejection fraction: a sex-stratified cross-sectional analysis.","authors":"Sophia Marie-Theres Dinges, Edzard Schwedhelm, Flavia Baldassarri, Bernhard Haller, Andreas B Gevaert, Rainer Böger, Ephraim B Winzer, Frank Edelmann, Ulrik Wisløff, Volker Adams, Burkert Pieske, Emeline M Van Craenenbroeck, Martin Halle, Susanna M Hofmann, Stephan Mueller-Stegner","doi":"10.1186/s13293-026-00944-3","DOIUrl":"10.1186/s13293-026-00944-3","url":null,"abstract":"","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13335291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395633","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":"Circadian dysregulation as a factor in impaired hepatic protein-synthetic function under chronic photoperiod disruption: the role of sex and chronobiotic correction.","authors":"David A Areshidze, Maria A Kozlova, Anna I Anurkina, Valery P Chernikov, Nikita S Gladyshev","doi":"10.1186/s13293-026-00949-y","DOIUrl":"10.1186/s13293-026-00949-y","url":null,"abstract":"<p><strong>Background: </strong>Liver metabolism is under tight control of the circadian system. Disruption of key clock gene expression (desynchronosis) leads to the misalignment of metabolic pathways. However, the relationship between circadian dysregulation and hepatic protein-synthetic function, as well as its sexual dimorphism, remains poorly understood. To evaluate the effect of chronic photoperiod disruption on hepatic protein-synthetic function (total protein, albumin) and to establish its relationship with the expression of key circadian proteins (BMAL1, CLOCK, PER2) in male and female rats, as well as to assess the efficacy of exogenous melatonin in correcting the identified disturbances.</p><p><strong>Methods: </strong>The study was performed on 240 adult Wistar rats (120 males, 120 females). Animals were divided into 3 groups: control (light: dark 10:14 h), dark deprivation (LL, constant light for 21 days), and LL + melatonin (12 mg/L drinking water). Plasma levels of total protein and albumin were measured. Immunohistochemistry was used to assess the percentage of positively stained hepatocytes for BMAL1, CLOCK, and PER2. Statistical analysis included two-way ANOVA, Pearson correlation analysis, ANCOVA, and ROC analysis.</p><p><strong>Results: </strong>Dark deprivation reduced albumin levels by 15.7% in males and by 15.9% in females compared to controls. Two-way ANOVA revealed significant effects of \"lighting conditions\" (F = 145.3, p < 0.0001), \"sex\" (F = 18.7, p < 0.01), and their interaction (F = 7.2, p < 0.05). BMAL1 and CLOCK expression decreased by more than 70% in both sexes, whereas PER2 expression paradoxically increased by 28.9-35.0%. Strong correlations were found between albumin levels and expression of BMAL1 (r = 0.79-0.81, p < 0.001), CLOCK (r = 0.69-0.74, p < 0.001), and PER2 (r= - 0.68 to - 0.71, p < 0.001). ANCOVA (R²=0.71, p < 0.0001) identified BMAL1 expression as the most significant independent predictor of albumin levels (β = 0.52, p < 0.0001), with sex retaining independent significance (p = 0.02). ROC analysis demonstrated high predictive performance of BMAL1 expression for hypoalbuminemia (AUC = 0.87-0.89, p < 0.0001). Melatonin treatment fully restored the expression of all examined circadian proteins and normalized protein synthetic parameters to control levels in both sexes.</p><p><strong>Conclusion: </strong>Chronic photoperiod disruption induces profound hepatic desynchronosis characterized by suppression of BMAL1/CLOCK and accumulation of PER2, which is associated with decreased protein synthetic function. A pronounced sexual dimorphism in susceptibility to desynchronosis was identified. BMAL1 expression is a highly informative predictor of hypoalbuminemia. Exogenous melatonin fully restores the impaired parameters, supporting its use as an effective chronobiotic.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387222","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":"Sexually-dimorphic offspring outcomes following antenatal corticosteroids: a review of the evidence for congenital adrenal hyperplasia and preterm birth risk.","authors":"Lulu Y L Birch, Amanda N Sferruzzi-Perri","doi":"10.1186/s13293-026-00938-1","DOIUrl":"10.1186/s13293-026-00938-1","url":null,"abstract":"<p><strong>Background: </strong>Pregnant individuals may receive antenatal corticosteroids for various conditions, including congenital adrenal hyperplasia (to prevent virilisation in female fetuses) and preterm birth risk (to hasten fetal maturation and improve perinatal survival). This narrative review aimed to evaluate the evidence of sexually-dimorphic offspring outcomes following antenatal corticosteroids for such conditions and explore the potential underlying mechanisms.</p><p><strong>Methods: </strong>A comprehensive MEDLINE search identified twenty-eight studies for inclusion: seven focused on congenital adrenal hyperplasia and twenty-one focused on preterm birth risk.</p><p><strong>Results: </strong>For congenital adrenal hyperplasia, evidence suggests that antenatal corticosteroids are associated with sexually-dimorphic outcomes across cognition, behaviour and brain structure. Females demonstrated more consistently negative outcomes, particularly within the congenital adrenal hyperplasia-affected population, where females were exposed to longer treatment durations than males. The outcomes for males were more heterogenous. For preterm birth, some studies suggest preterm males remain at increased risk for mortality and morbidity, while in term-born infants, females may have worse outcomes. The nature of these effects, however, differed with antenatal corticosteroid types, and conflicting findings also existed. Potential mechanisms for sexually-dimorphic outcomes include differences in placental enzyme and receptor expression and activity, fetal hypothalamic-pituitary-adrenal (HPA) axis function, and susceptibility to developing respiratory conditions.</p><p><strong>Conclusions: </strong>The current literature suggests potential sex differences following antenatal corticosteroids, which differ between congenital adrenal hyperplasia and preterm birth risk. Owing to surmounting evidence of negative outcomes and the retracting use of antenatal corticosteroids for congenital adrenal hyperplasia, further research will be challenging. Whereas studies concerning sexually-dimorphic responses to antenatal corticosteroids for preterm birth risk are essential, given their widespread use. Further research in this area may help to understand whether the clinical management of preterm birth should be adjusted according to sex.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381238","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":"Neonatal estradiol influences regional gene expression for early sex-specific inflammatory responses in the 5xFAD mouse model.","authors":"Phaedra R Keller-Norrell, Brad T Casali, Logan N Yost, Erin G Reed","doi":"10.1186/s13293-026-00948-z","DOIUrl":"10.1186/s13293-026-00948-z","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD), the most prevalent form of dementia, exhibits a strong sex bias, with women comprising two-thirds of all patients, for reasons that remain unclear. Microglia, as the brain's resident immune cell, are key players in AD pathogenesis and are increasingly understood as being sex-specific. However, the mechanisms underlying these differences, and how they may in turn contribute to distinct pathogenesis has not been well examined. Therefore, this study aimed to investigate the organizational role of neonatal estradiol (E2) in early-life sex-patterning of microglia for disease onset and progression.</p><p><strong>Methods: </strong>We assessed the effect of neonatal estradiol exposure on microglial and neuronal density, microgliosis, and gene expression related to microglial identity and responses using immunohistochemistry, qPCR, and ProteinSimple Jess on-capillary immunoblotting.</p><p><strong>Results: </strong>We find neonatal estradiol administration influences the expression of genes and proteins involved in inflammation and X chromosome inactivation, without affecting cellular composition of the cortex and hippocampus. Additionally, we observed genotype-dependent changes to the female reproductive cycle in E2 treated 5xFAD females.</p><p><strong>Conclusions: </strong>Overall, the results of the present study provide novel insight into the role of steroid sex hormones in neonatal microglial programing, and how this programming may set the stage for further sex- and disease-linked alterations later in life.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381695","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}