Biology of Sex Differences最新文献

{"title":"Sex differences in a mouse model of radiation-induced cardiomyopathy.","authors":"Emily R Whelan, Evan E Perona, Jessica J Fliess, S Christian Kocsis, Gabriel J Weigel, Elizabeth J McCabe, Charwan Hamilton, Damian N Di Florio, Varsini Balamurugan, Danielle J Beetler, Logan P Macomb, Max W Strandes, Frances C Wilson, Emma F Murphy, Ashley A Darakjian, Molly M Watkins, Alayna M Puls, Cameron J Hartmoyer, Natalie Bonvie-Hill, Sami Khatib, Chris J McLeod, Jordan C Ray, Michael D Story, Steven M Herchko, Bradford S Hoppe, DeLisa Fairweather","doi":"10.1186/s13293-026-00998-3","DOIUrl":"10.1186/s13293-026-00998-3","url":null,"abstract":"<p><strong>Background: </strong>Radiation-induced heart disease (RIHD) may develop months to years following radiation therapy for cancers near the heart such as lung or breast cancer. Several mouse models of RIHD exist to study the pathogenesis of disease, but to our knowledge no studies have examined whether sex differences exist in RIHD in mice.</p><p><strong>Methods: </strong>Female and male BALB/cJ mice received a single whole-heart dose of 22 Gy (Gy) radiation via a C5 collimator vs. sham controls that received 0 Gy, anesthesia and were placed in the X-ray machine for the same length of time. Endpoints were examined at 24 h (innate), day 10 (acute) and day 35 (chronic) post irradiation.</p><p><strong>Results: </strong>Females and males developed dsDNA breaks from radiation at day 10 but females had more damage than males (p < 0.001). Vessel area and wall thickness were increased by radiation at day 10 and 35 but vessel area was greater in irradiated males than females at day 35 (p = 0.003). Bulk RNA sequencing of the heart at day 10 revealed that females and males developed similar gene pathway responses to radiation by upregulating cellular repair pathways and developing mitochondrial dysfunction. However, females upregulated the master regulator of mitochondrial function, Pgc1α (p = 0.0001), suggesting possible improved mitochondrial repair in females. By day 35, females developed mild cardiomyopathy while males developed myocardial and perivascular fibrosis and inflammatory dilated cardiomyopathy (iDCM).</p><p><strong>Conclusions: </strong>We observed sex differences in most cardiac parameters that we examined following radiation exposure. BALB/c males exposed to 22 Gy radiation developed iDCM by day 35 while females developed mild cardiomyopathy. Further research is needed to better understand mechanisms driving sex differences in RIHD using translational animal models.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163953","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 and age at exposure influence ¹³¹I biodistribution and dosimetry in Sprague-Dawley rats.","authors":"Anja Schroff, Klara Insulander Björk, Nishte Rassol, Julia Johansson, Torgny Lundberg, Hana Bakr, Martin Andersson, Johan Spetz, Eva Forssell-Aronsson","doi":"10.1186/s13293-026-00989-4","DOIUrl":"10.1186/s13293-026-00989-4","url":null,"abstract":"<p><strong>Background: </strong>Assessing the biodistribution and absorbed dose of ¹³¹I is crucial for optimisation of radionuclide therapy, as well as for improving risk assessment following nuclear emergencies. After the Chernobyl accident, an increase in thyroid cancer among children was observed in regions affected by ¹³¹I fallout, particularly among young girls. Reasons for these age- and sex-specific differences in response to low doses of ¹³¹I are not fully understood, but variations in biodistribution and absorbed dose may be contributing factors. The aim of this study was therefore to assess the influence of sex and age at exposure on the biodistribution and dosimetry of ¹³¹I.</p><p><strong>Methods: </strong>Male and female Sprague Dawley rats were internally exposed to 0.36 MBq ¹³¹I at 5 or 17 weeks of age, corresponding to young and adult exposure groups. The ¹³¹I activity concentration of 16 vital tissues was measured at six time points (1-144 h post-injection) and used to estimate the mean absorbed dose to each organ. Sodium-iodide symporter (NIS) protein expression was assessed using immunohistochemistry and western blot.</p><p><strong>Results: </strong>The thyroid showed the highest ¹³¹I activity concentration at 18 h in males and 24 h in females, regardless of age. All non-thyroid tissues showed substantially lower activity concentrations, with the stomach having the second-highest levels. Statistically significant sex differences were determined in all tissues, with the most pronounced effect in the thyroid, where females consistently had higher activity concentrations compared to males. Age at exposure also impacted the biodistribution in some tissues. These differences led to pronounced variations in the absorbed dose. The absorbed dose to the thyroid ranged from 23 Gy/MBq in adult males to 100 Gy/MBq in young females. Protein quantification of NIS showed high individual variability but no clear difference between the groups.</p><p><strong>Conclusions: </strong>The results demonstrate that sex and age at exposure affect ¹³¹I biodistribution and absorbed dose in rats, particularly in the thyroid. The observed differences in absorbed dose may partly explain the variation in susceptibility to thyroid cancer in exposed populations reported after the Chernobyl accident. Further research is needed to clarify the underlying biological and mechanistic drivers of these differences.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011849","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 ferroptosis-related vulnerability to autism-like deficits in the adolescent medial prefrontal cortex following embryonic valproic acid exposure.","authors":"Shatong Zhao, Jing Wang, Yi Pan, Ying Yang, Yifei Yin, Wu Li, Jiangshan Li, Xiang Feng","doi":"10.1186/s13293-026-00982-x","DOIUrl":"10.1186/s13293-026-00982-x","url":null,"abstract":"<p><strong>Background: </strong>Prenatal valproic acid (VPA) exposure is an important environmental risk factor for autism spectrum disorder (ASD), but the mechanisms underlying VPA-induced ASD-like phenotypes remain unclear. Emerging evidence implicates neuronal ferroptosis and neurodevelopmental disturbances, yet whether these alterations vary across developmental stages and between sexes is unknown.</p><p><strong>Methods: </strong>Adolescent male and female C57BL/6 mice exposed to VPA at embryonic day 12.5 (E12.5) or postnatal day 14 (PND14) were used to examine behavioral and neurobiological effects of VPA exposure across developmental stages and between sexes. Sociability and anxiety-like behaviors were assessed using the three-chamber social interaction test (3-CT) and open field test (OFT), respectively. Histological alterations in the medial prefrontal cortex (mPFC), hippocampus, and striatum were examined using hematoxylin-eosin (HE) and Nissl staining. Ferroptosis-related changes were evaluated using biochemical assays, immunofluorescence, transmission electron microscopy and Western blotting. In male mice, the effects of prenatal and early postnatal VPA exposure were compared to assess whether similar behavioral and ferroptosis-related alterations were observed across developmental windows.</p><p><strong>Results: </strong>Both male and female adolescent offspring exposed to VPA exhibited social deficits and anxiety-like behaviors, with a more pronounced behavioral deficits in males, particularly in social preference and sociability. Histological analysis revealed variable degrees of neuronal abnormalities in the mPFC and hippocampus of VPA-exposed offspring, with the most prominent alterations observed in the mPFC. These histological changes were observed in both male and female offspring. Ferroptosis-related molecular changes were most evident in the mPFC and were accompanied by mitochondrial abnormalities and vacuolization. These alterations exhibited a distinct pattern of sex differences, with more pronounced changes observed in males than in females. Additionally, in male offspring, prenatal and early postnatal VPA exposure were associated with similar patterns of behavioral abnormalities and ferroptosis-related changes in the mPFC.</p><p><strong>Conclusion: </strong>This study suggests that prenatal VPA exposure induces ferroptosis-related abnormalities which could be linked to ASD-like behavioral and functional impairments, with more pronounced changes observed in male offspring. Among the brain regions examined, the mPFC showed the most prominent neurohistological and ferroptosis-related alterations. In male mice, prenatal and early postnatal VPA exposure were associated with similar patterns of ferroptosis-related molecular alterations, suggesting that ferroptosis-assiociated alterations may represent a shared molecular feature of VPA-induced neurodevelopmental abnormalities across different developmental windows.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975679","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 face looking preferences at birth.","authors":"Yumnah T Khan, Alex Tsompanidis, Eden Hymanson, Sehanya Wickramanayake, Apex Consortium, Topun Austin, Carrie Allison, Simon Baron-Cohen","doi":"10.1186/s13293-026-00976-9","DOIUrl":"10.1186/s13293-026-00976-9","url":null,"abstract":"<p><p>While sex differences in behaviour have attracted considerable scientific interest, their underlying causes are complex and remain poorly understood. One approach to understand whether early biological factors might play a partial role is to study newborns, who have limited postnatal experiences. Previous research on neonatal sex differences is extremely limited, and studies that do exist have yielded mixed results, raised methodological concerns, and are yet to be replicated. To assess these gaps, the present study aimed to reevaluate sex differences in neonatal attention. 130 neonates (67 males, 63 females; mean age = 33 h) were presented with a video of a human face and a non-social object. When analysing percentage looking times, on average, females allocated a greater percentage of time looking at the face relative to males (d = 0.40). When analysing absolute looking times, females showed a preference for the face compared to the non-social object, while males showed no preference for either. However, no differences were observed between males' and females' absolute looking times for the face or object, indicating that sex differences are most prominent in the relative allocation of attention. Since sex differences in relative attentional patterns are present from the earliest days of life, one possible explanation for this effect may be due to contributions from prenatal factors (e.g., sex hormones). However, alternative explanations may be that these differences reflect general maturational differences between males and females or arise from low-level visual properties of the stimuli rather than their social versus non-social content.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015509","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":"Genome-wide association study of sarcopenia index reveals sex-stratified genetic architecture.","authors":"Yumeng Mu, Binzhi Liao, Mengliang Luo, Kaifeng Lu, Huaxin Tang, Mao Nie, Xianding Sun","doi":"10.1186/s13293-026-00973-y","DOIUrl":"10.1186/s13293-026-00973-y","url":null,"abstract":"<p><strong>Background: </strong>The sarcopenia index (SI), defined as the ratio of serum creatinine to cystatin C, is a proposed biomarker of muscle mass and sarcopenia, yet its genomic basis and genetic architecture remain largely unexplored.</p><p><strong>Methods: </strong>We performed combined-sex and sex-stratified genome-wide association studies of SI in the UK Biobank. We examined the overlap between SI-associated loci and loci previously reported for sarcopenia-related traits. We assessed sexually dimorphic effects and gene-sex interactions, performed fine-mapping, and conducted credible gene prioritization, motif and transcription factor binding enrichment, gene-set enrichment, linkage disequilibrium score regression, and cross-phenotype colocalization.</p><p><strong>Results: </strong>We identified 774 unique independent SI-associated loci across all analyses, with 747 detected in the combined-sex GWAS, 283 in the male-stratified GWAS, and 311 in the female-stratified GWAS; 367 of these loci had not been previously reported for conventional sarcopenia-related traits. Sex-stratified analyses highlighted the rs1145093-chr15q21.1-GATM region, where CARMA identified sex-differentiated causal variants. We prioritized 17 male-biased and 11 female-biased credible genes. Enrichment analyses implicated androgen receptor and GATA4 in males, and ESR1 and MYOD1 in females. Enrichment revealed shared pathways involving inflammation, cellular stress, and aging-related processes. LDSC showed inverse genetic correlations between SI and heart failure (rg = -0.19, p = 2.30 × 10^{- 9}) and metabolic syndrome (rg = -0.12, p = 8.49 × 10^{- 8}), and a positive correlation with chronic kidney disease. Compared with female SI, male SI exhibited two additional loci showing colocalization with four metabolic traits.</p><p><strong>Conclusions: </strong>These findings clarify the genetic architecture of SI and reveal sex-dependent mechanisms underlying sarcopenia, supporting precision risk assessment and targeted interventions.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900111","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 microvascular patterns associated with low- and high-risk for cardiovascular disease.","authors":"Elin Nyman, Rasmus Magnusson, Tomas Strömberg, Carl Johan Östgren, Sara Bergstrand, Hanna Jonasson","doi":"10.1186/s13293-026-00955-0","DOIUrl":"10.1186/s13293-026-00955-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The role of the microcirculation in cardiovascular health in males and females is not fully understood. Skin microvascular function can be assessed non-invasively by measuring the response to a brief occlusion of the arm, which produces a hyperemic response that depends on multiple regulatory pathways. Whether the resulting time-resolved microvascular parameters discriminate between low- and high-cardiovascular-risk individuals, and whether the informative features differ between males and females, is not known.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;We analyzed time-resolved skin microcirculatory hemoglobin oxygen saturation and perfusion measured using a combined system integrating laser Doppler flowmetry and diffuse reflectance spectroscopy during a standardized occlusion-release protocol (including baseline, occlusion and reperfusion phases with a total duration of 20 min) in 3,177 participants in the Swedish CArdioPulmonary bioImage Study (SCAPIS) microvascular sub-study. Participants were stratified into a low-risk group (Systematic COronary Risk Evaluation 2 (SCORE2) &lt; 5%, no diabetes or previous atherosclerotic cardiovascular disease (ASCVD); n = 1,645) and a high-risk group (SCORE2 &gt; 7.5%, or diabetes, or previous ASCVD, or severe chronic kidney disease; n = 761). Random forest classifiers were trained to discriminate low- from high-risk individuals using the full time-resolved signals, in the combined cohort and separately by sex, with feature importance mapped back to the time axis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The classifier achieved area under the curve (AUC) of 0.685 (95% confidence interval (CI): 0.663-0.707) in the full cohort (i.e. including both females and males). Discrimination was primarily driven by the post-occlusion hyperemic phase of oxygen saturation, with lower responses observed in high-risk individuals compared to low-risk individuals. Sex-stratified models achieved similar performance in females (AUC 0.638, 95% CI: 0.596-0.679) and males (AUC 0.644, 95% CI: 0.628-0.660). In males, both perfusion and oxygen saturation contributed to risk discrimination, with low-risk individuals exhibiting a more pronounced hyperemic perfusion response. In females, discrimination was driven mainly by oxygen saturation, while perfusion responses showed substantial overlap between risk groups and limited discriminatory value.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Time-resolved microvascular signals provide information for cardiovascular risk discrimination that differs between males and females. In both sexes, high-risk individuals exhibited an attenuated post-occlusion oxygen saturation response, indicating impaired microvascular reactivity. Perfusion contributed additional discriminatory information in males, but showed limited value in females. These findings suggest that perfusion and oxygen saturation reflect partly different aspects of microvascular regulation, with different relevance to cardiovascular ri","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13403894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148598383","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":"Unraveling circRNAs and ceRNA regulatory networks underlying sex-specific gametogenesis impairment in triploid Pacific oysters (Crassostrea gigas).","authors":"Lang Guo, Huihui Wang, Hong Yu, Qi Li","doi":"10.1186/s13293-026-00958-x","DOIUrl":"https://doi.org/10.1186/s13293-026-00958-x","url":null,"abstract":"<p><strong>Background: </strong>In the Pacific oyster Crassostrea gigas, triploidization-a well-established technique for generating sterile organisms-provides a promising model to study reproductive dysfunction, as it causes severe and sex-specific impairments in gametogenesis. Specifically, triploid males produce abundant spermatocytes and spermatids but fail to generate mature spermatozoa, while oogenesis in triploid females presents a more complex and heterogeneous picture. The molecular basis for this differential gametogenesis impairment, however, is not fully understood.</p><p><strong>Methods: </strong>To investigate the roles of circRNA and ceRNA networks in the sex-specific gametogenesis impairment of triploid oysters, gonadal circRNAs were identified and their expression was profiled from whole transcriptome data of diploid and triploid oysters. Differentially expressed circRNAs were then subjected to functional enrichment analysis. Competitive endogenous RNA (ceRNA) networks were constructed from the interactions of differentially expressed RNAs. Key candidate genes implicated in gametogenesis impairment were then identified and characterized through integrated bulk and single-nucleus RNA-seq analyses.</p><p><strong>Results: </strong>Differential expression analysis revealed substantial alterations in circRNAs expression between diploid and triploid gonads. Functional enrichment of circRNA source genes implicated global metabolic and cell proliferation pathways associated with oogenesis impairment, while it implicated lipid/steroid metabolism, cell proliferation, and apoptosis pathways associated with spermatogenesis disruption in triploid oysters. Sex-specific ceRNA networks were constructed for oogenesis and spermatogenesis, revealing extensive regulatory rewiring in triploid gonads. Analysis of bulk and single-nucleus RNA-seq data identified key candidate genes within these ceRNA networks. Specifically, upregulation of FoxG1, Sox11, Cyp2J6, and Tra2A in somatic cells, combined with downregulation of Uhrf1, Ccna2, Sox2, and Bre1 in germ cells, was implicated in oogenesis impairment of triploids. Similarly, the ceRNA-mediated suppression of Iqch, Ccdc173, Srebp1, and Gtpbp2 was linked to disrupted spermatogenesis.</p><p><strong>Conclusions: </strong>These findings highlight that circRNA-mediated ceRNA dysregulation is potentially associated with gametogenesis impairment in triploid oysters, and offer novel insights into post-transcriptional regulatory mechanisms underlying molluscan reproduction.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227065","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 the association of uric acid to HDL-cholesterol ratio (UHR) with subclinical cardiovascular damage.","authors":"Mariangela Rubino, Angela Palummo, Mattia Massimino, Carolina Averta, Stefania Belviso, Asia Servello, Francesco Maria Brisinda, Alberto Cosenza, Angela Sciacqua, Maria Perticone, Francesco Perticone, Elettra Mancuso, Gaia Chiara Mannino, Francesco Andreozzi","doi":"10.1186/s13293-026-00956-z","DOIUrl":"10.1186/s13293-026-00956-z","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular diseases remain the leading cause of global mortality, with risk increasing significantly in women post-menopause. Identifying accessible biomarkers for subclinical risk stratification is a clinical priority. The uric acid to HDL-cholesterol ratio (UHR) has emerged as a composite marker reflecting metabolic burden and reduced vascular protection. This study investigates the independent association between UHR and subclinical organ damage, exploring sex-specific differences.</p><p><strong>Methods: </strong>We analyzed 1,198 Caucasian subjects. Subclinical cardiovascular damage was evaluated via carotid intima-media thickness (c-IMT) and left ventricular mass index (LVMI). Multivariate linear regression and formal interaction analyses were employed to assess the independent association of UHR with organ damage, adjusting for traditional cardiometabolic risk factors.</p><p><strong>Results: </strong>UHR correlated significantly with adiposity, insulin resistance, blood pressure, and lipid profiles. In the total population, UHR was independently associated with both c-IMT (β = 0.093, p = 0.003) and LVMI (β = 0.194, p < 0.0001). A significant sex-UHR interaction was observed for LVMI (p = 0.024). Sex-stratified analyses revealed that UHR was linked to LVMI in women, particularly those postmenopausal, but not in males. In postmenopausal women, UHR remained an independent determinant of LVMI (β = 0.164, p = 0.033).</p><p><strong>Conclusions: </strong>UHR is independently associated with subclinical cardiovascular damage, displaying a sex-specific relationship with myocardial remodeling after menopause. As an inexpensive and easily accessible biomarker, UHR may represent a practical tool to combat clinical inertia and improve the early selection of postmenopausal women warranting targeted diagnostic workups.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"17 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149219886","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":"Hormonal status and reproductive life-course states as modulators of women's physiological responses to acute and chronic hypoxia: insights, challenges, and perspectives.","authors":"Ayoub Boulares, Olivier Dupuy, Nicola Luigi Bragazzi, Carina Enéa, Nathalie Delpech, Philippe Connes, Paul Robach, Samuel Vergès, Aurélien Pichon","doi":"10.1186/s13293-026-00954-1","DOIUrl":"10.1186/s13293-026-00954-1","url":null,"abstract":"<p><p>Hypoxia research has significantly advanced our understanding of how the human body responds to low-oxygen environments, yet women are still frequently studied without adequate consideration of hormonal status or reproductive life-course stage. This review examines the complex interactions between hormonal status across the female life course and the specific physiological responses of women to acute and chronic hypoxia, focusing on the menstrual cycle, hormonal contraception, pregnancy, menopausal status, hormone replacement therapy, gender-affirming hormone therapy, and reproductive health in high-altitude environments. Estrogen and progesterone significantly modulate ventilatory, cardiovascular, hematological, vascular, and muscular/metabolic responses to hypoxia, with distinct effects across different menstrual cycle phases, contraceptive regimens, and life-course states. Menopause introduces additional complexities, as declining hormone levels alter the body's ability to acclimatize to low-oxygen conditions. Additionally, we examine how chronic and lifelong hypoxia impacts reproductive health, including fertility and pregnancy outcomes, in women living at high altitudes, highlighting both physiological adaptations and contextual factors. While current research has made progress, further studies are needed to better understand these sex-specific responses. We propose that future research should integrate stratified approaches, accounting for hormonal status (cycle phase, contraceptive use, pregnancy, HRT, GAHT) and reproductive status, to optimize health and performance recommendations for women exposed to hypoxic environments.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148496967","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":"Vaginal microbiomes and their pertinent social context: a microbial ecological review proffering AMR-STI acquisition and emergence.","authors":"Samantha J Webster, Ian E Cock, Carney Matheson, Emma L Sweeney","doi":"10.1186/s13293-026-00953-2","DOIUrl":"10.1186/s13293-026-00953-2","url":null,"abstract":"<p><strong>Background: </strong>In the landscape of sexual health, sex, gender, and sexuality are inextricably linked and highly relevant to sexually transmitted infections (STIs). Globally, key sexual and reproductive health concerns of women have been associated with the socioeconomic status of their country, indicating that social context bears influence over sexual health outcomes. Further, the increasing prevalence of antimicrobial resistant STIs (AMR-STIs) in the sexual networks of gay and bisexual men-who-have-sex-with-men (GBMSM) suggests an implicit connection between microbiological and social phenomena, although research to date is relatively limited and often fails to reflect the complexity and nuance of sexual networks. Vulval and vaginal microbiome composition may influence STI acquisition and transmission, yet the relationships between composition, microenvironment, and STIs remain largely overlooked, especially in the context of women and gender-diverse people. In this article, we explore the possibility that a combination of social, sexual, and behavioural factors, combined with biological features, shape the microbiological context of STIs within the vaginal microenvironment. MAIN: The human vaginal microbiome (VMB) forms an ecological niche home to a complex ecosystem of microorganisms. The microbial composition of the VMB is diverse between individuals, with variations observed across racial and ethnic groups, and intrapersonal fluctuations linked to a plethora of factors both within and outside of personal control. Importantly, VMB health is a crucial component of wellbeing for people assigned female at birth (AFAB), transgendered women with neovaginas, and their sexual partners. Clinical context also remains important; in Australia, doxycycline prophylaxis (Doxy-PEP) has recently become available to GBMSM networks aimed to protect against the acquisition of STIs. However, Doxy-PEP guidelines exclude AFAB people and fail to specify regarding use among gender diverse individuals. Given the high prevalence of AMR-STIs within GBMSM networks, the impact of this intervention on excluded partners should be thoroughly investigated. Factors in the VMB such as biofilm formation and necessary microbial balance with opportunistic pathogens renders this ecological microbial niche a hypothetically perfect platform for AMR development and emergence within the social context.</p><p><strong>Conclusion: </strong>This review explores the social context of vaginal microbiomes, their potential influence on AMR-STI development, and highlight several important knowledge gaps to benefit from further research.</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/PMC13647661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444300","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}