Biology of Sex Differences最新文献

{"title":"Mapping the hippocampal spatial proteomic signature in male and female mice of an early Alzheimer's disease model.","authors":"Ana Contreras, Raquel Jiménez-Herrera, Souhail Djebari, Juan D Navarro-López, Lydia Jiménez-Díaz","doi":"10.1186/s13293-025-00697-5","DOIUrl":"10.1186/s13293-025-00697-5","url":null,"abstract":"<p><strong>Background: </strong>Hippocampal dysfunction induced by soluble amyloid-β oligomers (oAβ) is an early neuropathological hallmark of Alzheimer's disease (AD). oAβ shifts hippocampal synaptic-plasticity induction threshold facilitating long-term depression (LTD) instead of long-term potentiation (LTP, the functional basis of memory), thereby leading to memory deficits in early AD-like amyloidosis mouse models. In this regard, the spatial distribution of the underlying synaptic-plasticity/memory proteome changes in the hippocampus, and potential sex differences, remain unknown. Here we postulated that some protein changes related to synaptic-plasticity and memory may be unique to sex and/or specific to the dorsal or ventral hippocampus -as both regions have distinct functionality and connectivity-, potentially providing sex- and spatial-specific proteomic phenotypes for early AD-amyloidosis interventions.</p><p><strong>Methods: </strong>An innovative spatial-resolution proteomics study was performed to map whole hippocampal proteome distribution using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry. For this purpose, sixteen adult male and female mouse brains intracerebroventricularly injected with oAβ_1-42/vehicle were analyzed. MALDI-imaging RapifleXTM-MALDI-TissuetyperTM TOF/TOF mass spectrometer was used, followed by traditional tandem mass spectrometry (MS/MS) for precise protein identification on tissue.</p><p><strong>Results: </strong>34 proteins showed significant differences in expression levels due to treatment, sex, or hippocampal location among 234 peptides initially detected; and displayed significant protein-protein interaction (PPI), indicating main functional relationship to LTP/LTD pathways and memory. Thus, 14 proteins related to synaptic-plasticity and/or AD were further studied, showing that most modulated glycogen synthase kinase-3β (GSK-3β), a protein widely involved in synaptic-plasticity induction threshold regulation towards LTD. Accordingly, hippocampal GSK-3β was found to be overactivated in AD-like amyloidosis mice.</p><p><strong>Conclusions: </strong>We show for the first-time specific sex-dependent synaptic-plasticity proteome changes in dorsal/ventral hippocampi that modulate GSK-3β activity. These findings provide new insight into the early amyloidosis pathogenesis in AD and offer valuable, unique proteomic phenotypes as potential biomarkers and targets for early diagnosis and therapy in both sexes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"36"},"PeriodicalIF":4.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141410","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-related differences and associated transcriptional signatures in the brain ventricular system and cerebrospinal fluid development in full-term neonates.","authors":"Yuxin Sun, Chenxin Fu, Lifan Gu, Huifang Zhao, Yuying Feng, Chao Jin","doi":"10.1186/s13293-025-00719-2","DOIUrl":"10.1186/s13293-025-00719-2","url":null,"abstract":"<p><strong>Background: </strong>The cerebrospinal fluid (CSF) is known to serve as a unique environment for neurodevelopment, with specific proteins secreted by epithelial cells of the choroid plexus (CP) playing crucial roles in cortical development and cell differentiation. Sex-related differences in the brain in early life have been widely identified, but few studies have investigated the neonatal CSF system and associated transcriptional signatures.</p><p><strong>Methods: </strong>This study included 75 full-term neonates [44 males and 31 females; gestational age (GA) = 37-42 weeks] without significant MRI abnormalities from the dHCP (developing Human Connectome Project) database. Deep-learning automated segmentation was used to measure various metrics of the brain ventricular system and CSF. Sex-related differences and relationships with postnatal age were analyzed by linear regression. Correlations between the CP and CSF space metrics were also examined. LASSO regression was further applied to identify the key genes contributing to the sex-related CSF system differences by using regional gene expression data from the Allen Human Brain Atlas.</p><p><strong>Results: </strong>Right lateral ventricles [2.42 ± 0.98 vs. 2.04 ± 0.45 cm3 (mean ± standard deviation), p = 0.036] and right CP (0.16 ± 0.07 vs. 0.13 ± 0.04 cm3, p = 0.024) were larger in males, with a stronger volume correlation (male/female correlation coefficients r: 0.798 vs. 0.649, p < 1 × 10^- 4). No difference was found in total CSF volume, while peripheral CSF (male/female β: 1.218 vs. 1.064) and CP (male/female β: 0.008 vs. 0.005) exhibited relatively faster growth in males. Additionally, the volumes of the lateral ventricular system, third ventricle, peripheral CSF, and total CSF were significantly correlated with their corresponding CP volume (r: 0.362 to 0.799, p < 0.05). DERL2 (Degradation in Endoplasmic Reticulum Protein 2) (r = 0.1319) and MRPL48 (Mitochondrial Large Ribosomal Subunit Protein) (r=-0.0370) were identified as potential key genes associated with sex-related differences in CSF system.</p><p><strong>Conclusion: </strong>Male neonates present larger volumes and faster growth of the right lateral ventricle, likely linked to corresponding CP volume and growth pattern. The downregulation of DERL2 and upregulation of MRPL48 may contribute to these sex-related variations in the CSF system, suggesting a molecular basis for sex-specific brain development.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"35"},"PeriodicalIF":4.9,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141412","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 the modulation of anxiety- and depression-like behaviors by matrix metalloproteinase-9 expression levels in mice.","authors":"Júlia Senserrich, Elena Castro, Eva Florensa-Zanuy, Álvaro Díaz, Ángel Pazos, Albert Adell, Athina Tzinia, Fuencisla Pilar-Cuéllar","doi":"10.1186/s13293-025-00716-5","DOIUrl":"10.1186/s13293-025-00716-5","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder is one of the main causes of disability worldwide, but its etiopathology remains largely unknown, although several hypotheses have been proposed. Recent studies suggest a potential role for matrix metalloproteinase 9 (MMP-9) in depression, as it is overexpressed in the plasma of depressed patients and normalizes following chronic antidepressant treatment. This study aimed to characterize anxiety and depression-like behaviors in transgenic MMP-9 mice, as well as the expression of different neuroplasticity markers associated with depression, in both sexes.</p><p><strong>Methods: </strong>In this study, we characterized the behavioral phenotypes of both MMP-9 knockout and MMP-9-overexpressing male and female mice. Here, we used a battery of tests to assess anxiety (open field, light‒dark box, elevated plus maze, and novelty‒suppressed feeding tests), depressive-like (tail suspension and social interaction tests), and cognitive (T-maze) behaviors.</p><p><strong>Results: </strong>MMP-9 knockout female mice displayed increased innate anxiety (open field test), decreased behavioral despair (tail suspension test). Compared with control mice, female MMP-9 knockout mice presented increased levels of different neuroplasticity markers in the hippocampus. With respect to MMP-9-overexpressing mice, females presented decreased innate anxiety (elevated plus maze). Male MMP-9-overexpressing mice presented greater conflict-based anxiety (novelty-suppressed feeding test) than control mice did.</p><p><strong>Conclusions: </strong>MMP-9 activity modifies anxiety- and depression-like behaviors, as well as neuroplasticity markers, in female but not in male mice. These findings reinforce the sex differences in the etiopathology of depression.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"34"},"PeriodicalIF":4.9,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126492","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 role of sex differences in cardiovascular, metabolic, and immune functions in health and disease: a review for \"Sex Differences in Health Awareness Day\".","authors":"Lana McClements, Alexandra Kautzky-Willer, Georgios Kararigas, Sofia B Ahmed, John N Stallone","doi":"10.1186/s13293-025-00714-7","DOIUrl":"10.1186/s13293-025-00714-7","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Sexual dimorphism is a fundamental characteristic of the anatomy and physiology of animals and humans, yet biomedical research has largely ignored these phenomena in the study of health and disease, despite early studies in the eighteenth and nineteenth centuries that demonstrated the importance of sex differences. With the explosive growth of biomedical research following World War II, especially in the 1970s through the 1990s, preclinical and clinical studies led to a greater recognition of sex differences in physiological function, particularly the significant disparities in the incidence of and mortality from cardiovascular diseases, which generally occur more frequently in men than in premenopausal women. There is a growing awareness that metabolic and immune dysfunction are intimately tied to the development of cardiovascular diseases. Thus, this review article focuses on sexual dimorphism in cardiovascular, metabolic, and immune function in health and disease, and was prepared for the journal Biology of Sex Differences as part of its recognition of \"Sex Differences in Health Awareness Day.\" This article clearly reveals the striking importance of sex differences in cardiovascular, metabolic, and immune system functions in health and in the pathogenesis of disease processes, which likely involve a combination of effects of the sex chromosomes as well as the gonadal steroid hormones. In the developing fetus, fetal sex clearly influences the pathogenesis of the hypertensive diseases of pregnancy, and sex differences in the effects of the fetus continue beyond pregnancy and appear to influence the future risk of maternal cardiometabolic diseases. Similarly, there is strong evidence of many clinically-relevant sexually dimorphic characteristics of obesity and type 2 diabetes mellitus which appear to involve both chromosomal and humoral effects, although the underlying pathophysiological mechanisms are poorly understood. The gonadal steroid hormones (both androgens and estrogens) are known to exert important effects on the regulation of intermediary metabolism; however, recent studies reveal the emerging importance of these hormones in the regulation of inflammation. For example, menopausal declines in estrogen are associated with increases in inflammatory markers and the development of heart failure in women. Similar effects on inflammatory function may also occur in men with progressive age-dependent declines in testosterone. Declines in androgen levels in men are also associated with detrimental effects on cardiovascular and metabolic function, especially the development of metabolic syndrome and type 2 diabetes, important risk factors for cardiovascular disease. Interestingly, pathophysiological increases in the normally lower testosterone levels in women are associated with the same detrimental effects on cardiovascular and metabolic function, revealing striking bi-directional sex differences in the effects of the androgens. Finally, i","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"33"},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976814","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 bladder cancer: understanding biological and clinical implications.","authors":"Prakash Chaudhary, Biplab Singha, Hany A Abdel-Hafiz, Maria Velegraki, Debasish Sundi, Swati Satturwar, Anil V Parwani, Sergei I Grivennikov, Sungyong You, Helen S Goodridge, Qin Ma, Yuzhou Chang, Anjun Ma, Bin Zheng, Dan Theodorescu, Zihai Li, Xue Li","doi":"10.1186/s13293-025-00715-6","DOIUrl":"10.1186/s13293-025-00715-6","url":null,"abstract":"<p><p>Bladder cancer (BC) remains a significant global health concern, with substantial sex and racial disparities in incidence, progression, and outcomes. BC is the sixth most common cancer among males and the seventeenth most common among females worldwide. Over 90% of BC cases are urothelial carcinoma (UC) with high degrees of pathological heterogeneity. Molecular subtyping of BC has also revealed distinct luminal, basal, and neuroendocrine subtypes, each with unique genetic and immune signatures. Emerging research uncovers the biasing effects of the sex hormones with androgens increasing BC risk through both tumor cell intrinsic and extrinsic mechanisms. The sex chromosomes, including both the X and Y chromosomes, also contribute to the sex differences in BC. The effect of sex chromosome is both independent from and synergistic with the effects of sex hormones. Loss of the Y chromosome is frequently observed in BC patients, while an extra copy of the X chromosome confers better protection against BC in females than in males. Advent of advanced technologies such as multiomics and artificial intelligence will likely further improve the understanding of sex differences in BC, which may ultimately lead to personalized preventative and treatment strategies depending on the biological sex of patients. This review delves into the impacts of biology of sex on BC, emphasizing the importance of further research into sex-specific biology to improve cancer prevention and care.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"31"},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961116","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 still matters for the brain and mental health across the lifespan.","authors":"Adriene M Beltz, Natalie C Tronson, Meharvan Singh, Samar Rezq","doi":"10.1186/s13293-025-00710-x","DOIUrl":"10.1186/s13293-025-00710-x","url":null,"abstract":"","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"32"},"PeriodicalIF":4.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952945","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 DNA methylation signatures of autism spectrum disorder from whole genome bisulfite sequencing of newborn blood.","authors":"Julia S Mouat, Nickilou Y Krigbaum, Sophia Hakam, Emily Thrall, George E Kuodza, Julia Mellis, Dag H Yasui, Piera M Cirillo, Yunin J Ludena, Rebecca J Schmidt, Michele A La Merrill, Irva Hertz-Picciotto, Barbara A Cohn, Janine M LaSalle","doi":"10.1186/s13293-025-00712-9","DOIUrl":"https://doi.org/10.1186/s13293-025-00712-9","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is a group of neurodevelopmental conditions currently diagnosed through behavioral assessments in childhood, though neuropathological changes begin in utero. ASD is more commonly diagnosed in males, a disparity attributed to both biological sex differences and diagnostic biases. Identifying molecular biomarkers, such as DNA methylation signatures, could provide more objective screening for ASD-risk in newborns, allowing for early intervention. Epigenetic dysregulation has been reported in multiple tissues from newborns who are later diagnosed with ASD, but this is the first study to investigate sex-specific DNA methylation signatures for ASD in newborn blood, an accessible and widely banked tissue.</p><p><strong>Methods: </strong>We assayed DNA methylation from newborn blood of ASD and typically developing (TD) individuals (discovery set n = 196, replication set n = 90) using whole genome bisulfite sequencing (WGBS). Sex-stratified differentially methylated regions (DMRs) were assessed for replication, comparisons by sex, overlaps with DMRs from other tissues, and enrichment for biological processes and SFARI ASD-risk genes.</p><p><strong>Results: </strong>We found that newborn blood ASD DMRs from both sexes significantly replicated in an independent cohort and were enriched for hypomethylation in ASD compared to TD samples, as well as location in promoters, CpG islands, and CpG island shores. By comparing female to male samples, we found that most sex-associated DMRs in TD individuals were also found in ASD individuals, alongside additional ASD-specific sex differences. Female-specific DMRs were enriched for X chromosomal location. Across both sexes, newborn blood DMRs overlapped significantly with DMRs from umbilical cord blood and placenta but not post-mortem cerebral cortex. DMRs from all tissues were enriched for neurodevelopmental processes (females) and known ASD genes (both sexes).</p><p><strong>Conclusions: </strong>Overall, we identified and replicated a sex-specific DNA methylation signature of ASD in newborn blood that supported the female protective effect and highlighted convergence of epigenetic and genetic signatures of ASD in newborns. Despite the study's limitations, particularly in female sample sizes, our results demonstrate the potential of newborn blood in ASD screening and emphasize the importance of sex-stratification in future studies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"30"},"PeriodicalIF":4.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963838","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":"ERβ mediates sex-specific protection in the App-NL-G-F mouse model of Alzheimer's disease.","authors":"Aphrodite Demetriou, Birgitta Lindqvist, Heba G Ali, Mohamed M Shamekh, Mukesh Varshney, Jose Inzunza, Silvia Maioli, Per Nilsson, Ivan Nalvarte","doi":"10.1186/s13293-025-00711-w","DOIUrl":"https://doi.org/10.1186/s13293-025-00711-w","url":null,"abstract":"<p><strong>Background: </strong>Menopausal loss of neuroprotective estrogen is thought to contribute to the sex differences in Alzheimer's disease (AD). Activation of estrogen receptor beta (ERβ) can be clinically relevant since it avoids the adverse systemic effects of ERα activation. However, very few studies have explored ERβ-mediated neuroprotection in AD, and no information on its contribution to the sex differences in AD exists. In the present study, we specifically explored the role of ERβ in mediating sex-specific protection against AD pathology in the App^NL-G-F knock-in mouse model of amyloidosis, and if surgical menopause (ovariectomy) modulates pathology in this model.</p><p><strong>Methods: </strong>We treated male and female App^NL-G-F knock-in mice with the clinically relevant and selective ERβ agonist LY500307. A subset of the females was ovariectomized prior to treatment. Y-maze and contextual fear conditioning tests were used to assess memory performance, and biochemical assays such as qPCR, immunohistochemistry, Western blot, and multiplex immunoassays, were used to evaluate amyloid pathology.</p><p><strong>Results: </strong>We found that Female App^NL-G-F mice had higher soluble Aβ levels in cortex and hippocampus than males and more activated microglia. ERβ activation protected against amyloid pathology and cognitive decline in both male and female App^NL-G-F mice. Although ovariectomy increased soluble amyloid beta (Aβ) in cortex and insoluble Aβ in hippocampus, as well as sustained neuroinflammation after ERβ activation, it had otherwise limited effects on pathology. We further identified that ERβ did not alter APP processing, but rather exerted its protection at least partly via microglia activation in a sex-specific manner.</p><p><strong>Conclusion: </strong>Combined, we provide new understanding to the sex differences in AD by demonstrating that ERβ protects against AD pathology differently in males and females, warranting reassessment of ERβ in combating AD.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"29"},"PeriodicalIF":4.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969931","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 response to A1BG loss results in female dilated cardiomyopathy.","authors":"James I Emerson, Wei Shi, Frank L Conlon","doi":"10.1186/s13293-025-00713-8","DOIUrl":"https://doi.org/10.1186/s13293-025-00713-8","url":null,"abstract":"<p><strong>Background: </strong>Cardiac disease often manifests with sex-specific differences in frequency, pathology, and progression. However, the molecular mechanisms underlying these differences remain incompletely understood. The glycoprotein A1BG has emerged as a female-specific regulator of cardiac structure and integrity, yet its precise role in the female heart is not well characterized.</p><p><strong>Methods: </strong>To investigate the sex-specific role of A1BG in the heart, we generated both a conditional A1bg knockout allele and an A1bg Rosa26 knockin allele. We employed histological analysis, electrocardiography, RNA sequencing (RNA-seq), transmission electron microscopy (TEM), western blotting, mass spectrometry, and immunohistochemistry to assess structural, functional, and molecular phenotypes.</p><p><strong>Results: </strong>Loss of A1BG in cardiomyocytes leads to persistent structural remodeling in female, but not male, hearts. Despite preserved systolic function in female A1bg^CM/CM mice left ventricular dilation and wall thinning are evident and sustained over time, consistent with early-stage dilated cardiomyopathy (DCM). Transcriptomic analyses reveal that A1BG regulates key metabolic pathways in females, including glucose-6-phosphate and acetyl-CoA metabolism. TEM imaging highlights sex-specific disruption of intercalated disc architecture in female cardiomyocytes. These findings suggest that the absence of A1BG initiates chronic pathological remodeling in female hearts, potentially predisposing them to DCM under stress or aging.</p><p><strong>Conclusion: </strong>A1BG is essential for maintaining ventricular structural integrity in female, but not male, hearts, leading to a chronic remodeling consistent with early-stage DCM.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"27"},"PeriodicalIF":4.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973191","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 role of androgens and global and tissue-specific androgen receptor expression on body composition, exercise adaptation, and performance.","authors":"Sabrina Tzivia Barsky, Douglas Ashley Monks","doi":"10.1186/s13293-025-00707-6","DOIUrl":"https://doi.org/10.1186/s13293-025-00707-6","url":null,"abstract":"<p><p>Gonadal testosterone stimulates skeletal muscle anabolism and contributes to sexually differentiated adipose distribution through incompletely understood mechanisms. Observations in humans and animal models have indicated a major role for androgen receptor (AR) in mediating sex differences in body composition throughout the lifespan. Traditional surgical, genetic and pharmacological studies have tested systemic actions of circulating androgens, and more recent transgenic approaches have allowed for tests of AR gene function in specific androgen responsive niches contributing to body composition, including: skeletal muscle and surrounding interstitial cells, white and brown adipose, as well as trabecular and cortical bone. Less well understood is how these functions of gonadal androgens interact with exercise. Here, we summarize the understood mechanisms of action of AR and its interactions with exercise, specifically on outcomes of body composition and muscle function, and the global- and tissue-specific role of AR in regulating skeletal muscle, adipose, and bone morphology. Additionally, we describe the known effects of androgen and AR manipulation on female body composition, muscle morphology, and sport performance, while highlighting a need for greater inclusion of female subjects in human and animal muscle physiology and endocrinology research.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"16 1","pages":"28"},"PeriodicalIF":4.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970800","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}