Biology of Sex Differences最新文献

{"title":"Sex Differences in Human Brain Structure at Birth.","authors":"Yumnah T Khan, Alex Tsompanidis, Marcin A Radecki, Lena Dorfschmidt, Topun Austin, John Suckling, Carrie Allison, Meng-Chuan Lai, Richard A I Bethlehem, Simon Baron-Cohen","doi":"10.1186/s13293-024-00657-5","DOIUrl":"10.1186/s13293-024-00657-5","url":null,"abstract":"<p><strong>Background: </strong>Sex differences in human brain anatomy have been well-documented, though remain significantly underexplored during early development. The neonatal period is a critical stage for brain development and can provide key insights into the role that prenatal and early postnatal factors play in shaping sex differences in the brain.</p><p><strong>Methods: </strong>Here, we assessed on-average sex differences in global and regional brain volumes in 514 newborns aged 0-28 days (236 birth-assigned females and 278 birth-assigned males) using data from the developing Human Connectome Project. We also assessed sex-by-age interactions to investigate sex differences in early postnatal brain development.</p><p><strong>Results: </strong>On average, males had significantly larger intracranial and total brain volumes, even after controlling for birth weight. After controlling for total brain volume, females showed significantly greater total cortical gray matter volumes, whilst males showed greater total white matter volumes. After controlling for total brain volume in regional comparisons, females had significantly increased white matter volumes in the corpus callosum and increased gray matter volumes in the bilateral parahippocampal gyri (posterior parts), left anterior cingulate gyrus, bilateral parietal lobes, and left caudate nucleus. Males had significantly increased gray matter volumes in the right medial and inferior temporal gyrus (posterior part) and right subthalamic nucleus. Effect sizes ranged from small for regional comparisons to large for global comparisons. Significant sex-by-age interactions were noted in the left anterior cingulate gyrus and left superior temporal gyrus (posterior parts).</p><p><strong>Conclusions: </strong>Our findings demonstrate that sex differences in brain structure are already present at birth and remain comparatively stable during early postnatal development, highlighting an important role of prenatal factors in shaping sex differences in the brain.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457116","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 prelimbic cortex calcium dynamics during stress and fear learning.","authors":"Ignacio Marin-Blasco, Giorgia Vanzo, Joaquin Rusco-Portabella, Lucas Perez-Molina, Leire Romero, Antonio Florido, Raul Andero","doi":"10.1186/s13293-024-00653-9","DOIUrl":"https://doi.org/10.1186/s13293-024-00653-9","url":null,"abstract":"<p><p>In recent years, research has progressively increased the importance of considering sex differences in stress and fear memory studies. Many studies have traditionally focused on male subjects, potentially overlooking critical differences with females. Emerging evidence suggests that males and females can exhibit distinct behavioral and neurophysiological responses to stress and fear conditioning. These differences may be attributable to variations in hormone levels, brain structure, and neural circuitry, particularly in regions such as the prefrontal cortex (PFC). In the present study, we explored sex differences in prelimbic cortex (PL) calcium activity in animals submitted to immobilization stress (IMO), fear conditioning (FC), and fear extinction (FE). While no significant sex differences were found in behavioral responses, we did observe differences in several PL calcium activity parameters. To determine whether these results were related to behaviors beyond stress and fear memory, we conducted correlation studies between the movement of the animals and PL activity during IMO and freezing behavior during FC and FE. Our findings revealed a clear correlation between PL calcium activity with movement during stress exposure and freezing behavior, with no sex differences observed in these correlations. These results suggest a significant role for the PL in movement and locomotion, in addition to its involvement in fear-related processes. The inclusion of both female and male subjects is crucial for studies like this to fully understand the role of the PFC and other brain areas in stress and fear responses. Recognizing sex differences enhances our comprehension of brain function and can lead to more personalized and effective approaches in the study and treatment of stress and fear-related conditions.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457117","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":"Isolated during adolescence: long-term impact on social behavior, pain sensitivity, and the oxytocin system in male and female rats.","authors":"Akseli P Graf, Anita C Hansson, Rainer Spanagel","doi":"10.1186/s13293-024-00655-7","DOIUrl":"https://doi.org/10.1186/s13293-024-00655-7","url":null,"abstract":"<p><strong>Background: </strong>Adolescent social isolation (ASI) has profound long-term effects on behavioral and neural development. Despite this, the specific long-term impact of ASI during different adolescent stages and across sexes remain underexplored.</p><p><strong>Methods: </strong>Our study addresses this gap by examining the effects of early- and late- adolescent social isolation on both male and female rats. Rats were either isolated (or group-housed) starting from PD 21 (early) or PD 42 (late) for three weeks and then rehoused into groups. In adulthood (PD 90), rats underwent a battery of tests: elevated plus-maze, open field, novel object recognition, social interaction and social recognition memory and hotplate tests. Finally, we analyzed oxytocin receptor binding in several regions in the brains of a second cohort of rats.</p><p><strong>Results: </strong>Both, male and female rats from the late adolescent social isolation (LASI) groups spent significantly less time interacting in the social interaction test. Additionally, we observed a general decrease in social recognition memory regardless of sex. Both male ASI groups demonstrated heightened thermal pain sensitivity, while the opposite was observed in early adolescent social isolation (EASI) female rats. In the brain, we observed changes in oxytocin receptor (OTR) binding in the paraventricular nucleus of the hypothalamus (PVN) and paraventricular nucleus of the thalamus (PVT) and central amygdala (CeA) with the largest changes in EASI and LASI female rats.</p><p><strong>Conclusion: </strong>Our model demonstrates long-lasting alterations on behavior and oxytocin receptor binding levels following ASI providing insights into the long-term effects of ASI in a time- and sex-specific manner.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457115","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":"Integration of long-read sequencing, DNA methylation and gene expression reveals heterogeneity in Y chromosome segment lengths in phenotypic males with 46,XX testicular disorder/difference of sex development.","authors":"Agnethe Berglund, Emma B Johannsen, Anne Skakkebæk, Simon Chang, Julia Rohayem, Sandra Laurentino, Arne Hørlyck, Simon O Drue, Ebbe Norskov Bak, Jens Fedder, Frank Tüttelmann, Jörg Gromoll, Jesper Just, Claus H Gravholt","doi":"10.1186/s13293-024-00654-8","DOIUrl":"10.1186/s13293-024-00654-8","url":null,"abstract":"<p><strong>Background: </strong>46,XX testicular disorder/difference of sex development (46,XX DSD) is a rare congenital condition, characterized by a combination of the typical female sex chromosome constitution, 46,XX, and a variable male phenotype. In the majority of individuals with 46,XX DSD, a Y chromosome segment containing the sex-determining region gene (SRY) has been translocated to the paternal X chromosome. However, the precise genomic content of the translocated segment and the genome-wide effects remain elusive.</p><p><strong>Methods: </strong>We performed long-read DNA sequencing, RNA sequencing and DNA methylation analyses on blood samples from 46,XX DSD (n = 11), male controls (46,XY; variable cohort sizes) and female controls (46,XX; variable cohort sizes), in addition to RNA sequencing and DNA methylation analysis on blood samples from males with Klinefelter syndrome (47,XXY, n = 22). We also performed clinical measurements on all 46,XX DSD and a subset of 46,XY (n = 10).</p><p><strong>Results: </strong>We identified variation in the translocated Y chromosome segments, enabling subcategorization into 46,XX DSD (1) lacking Y chromosome material (n = 1), (2) with short Yp arms (breakpoint at 2.7-2.8 Mb, n = 2), (3) with medium Yp arms (breakpoint at 7.3 Mb, n = 1), and (4) with long Yp arms (n = 7), including deletions of AMELY, TBLY1 and in some cases PRKY. We also identified variable expression of the X-Y homologues PRKY and PRKX. The Y-chromosomal transcriptome and methylome reflected the Y chromosome segment lengths, while changes to autosomal and X-chromosomal regions indicated global effects. Furthermore, transcriptional changes tentatively correlated with phenotypic traits of 46,XX DSD, including reduced height, lean mass and testicular size.</p><p><strong>Conclusion: </strong>This study refines our understanding of the genetic composition in 46,XX DSD, describing the translocated Y chromosome segment in more detail than previously and linking variability herein to genome-wide changes in the transcriptome and methylome.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387585","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":"Female-bias in systemic lupus erythematosus: How much is the X chromosome to blame?","authors":"Adriana A Vieira, Inês Almada-Correia, Joana Inácio, Patrícia Costa-Reis, S T da Rocha","doi":"10.1186/s13293-024-00650-y","DOIUrl":"https://doi.org/10.1186/s13293-024-00650-y","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE or lupus) is an immune-mediated disease associated with substantial medical burden. Notably, lupus exhibits a striking female bias, with women having significantly higher susceptibility compared to men, up to 14-fold higher in some ethnicities. Supernumerary X chromosome syndromes, like Klinefelter (XXY) and Triple X syndrome (XXX), also present higher SLE prevalence, whereas Turner syndrome (XO) displays lower prevalence. Taken together, SLE prevalence in different X chromosome dosage sceneries denotes a relationship between the number of X chromosomes and the risk of developing lupus. The dosage of X-linked genes, many of which play roles in the immune system, is compensated between males and females through the inactivation of one of the two X chromosomes in female cells. X-chromosome inactivation (XCI) initiates early in development with a random selection of which X chromosome to inactivate, a choice that is then epigenetically maintained in the daughter cells. This process is regulated by the X-Inactive-Specific Transcript (XIST), encoding for a long non-coding RNA, exclusively expressed from the inactive X chromosome (Xi). XIST interacts with various RNA binding proteins and chromatin modifiers to form a ribonucleoprotein (RNP) complex responsible for the transcriptional silencing and heterochromatinization of the Xi. This ensures stable silencing of most genes on the X chromosome, with only a few genes able to escape this process. Recent findings suggest that the molecular components involved in XCI, or their dysregulation, contribute to the pathogenesis of lupus. Indeed, nonrandom XCI, elevated gene escape from XCI, and the autoimmune potential of the XIST RNP complex have been suggested to contribute to auto-immune diseases, such as lupus. This review examines these current hypotheses concerning how this dosage compensation mechanism might impact the development of lupus, shedding light on potential mechanisms underlying the pathogenesis of the disease.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387584","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 symptoms following the administration of BNT162b2 mRNA COVID-19 vaccine in children below 5 years of age in Germany (CoVacU5): a retrospective cohort study.","authors":"Jeanne Moor, Nicole Toepfner, Wolfgang C G von Meißner, Reinhard Berner, Matthias B Moor, Karolina Kublickiene, Christoph Strumann, Cho-Ming Chao","doi":"10.1186/s13293-024-00651-x","DOIUrl":"https://doi.org/10.1186/s13293-024-00651-x","url":null,"abstract":"<p><strong>Background: </strong>Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany.</p><p><strong>Methods: </strong>This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10 µg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines.</p><p><strong>Results: </strong>The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3 µg BNT162b2, no sex differences were noted, but after a first dose of 5-10 µg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p < 0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p < 0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p < 0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms.</p><p><strong>Conclusions: </strong>Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies (German Clinical Trials Register ID: DRKS00028759).</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340541","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-dependent effects of acute stress and alcohol exposure during adolescence on mRNA expression of brain signaling systems involved in reward and stress responses in young adult rats.","authors":"Carlotta Gobbi, Laura Sánchez-Marín, María Flores-López, Dina Medina-Vera, Francisco Javier Pavón-Morón, Fernando Rodríguez de Fonseca, Antonia Serrano","doi":"10.1186/s13293-024-00649-5","DOIUrl":"https://doi.org/10.1186/s13293-024-00649-5","url":null,"abstract":"<p><strong>Background: </strong>Adolescent stress and alcohol exposure increase the risk of maladaptive behaviors and mental disorders in adulthood, with distinct sex-specific differences. Understanding the mechanisms underlying these early events is crucial for developing targeted prevention and treatment strategies.</p><p><strong>Methods: </strong>Male and female Wistar rats were exposed to acute restraint stress and intermittent alcohol during adolescence. We assessed lasting effects on plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, and mRNA expression of genes related to corticotropin releasing hormone (CRH), neuropeptide Y (NPY), corticoid, opioid, and arginine vasopressin systems in the amygdala and hypothalamus.</p><p><strong>Results: </strong>The main findings are as follows: (1) blood alcohol concentrations (BAC) increased after the final alcohol administration, but stressed males had lower BAC than non-stressed males; (2) Males gained significantly more weight than females; (3) Stressed females showed higher ACTH levels than non-stressed females, with no changes in males; (4) Stress increased CORT levels in males, while stressed, alcohol-treated females had lower CORT levels than non-stressed females; (5) CRH: Females had lower Crhr1 levels in the amygdala, while alcohol reduced Crhr2 levels in males but not females. Significant interactions among sex, stress, and alcohol were found in the hypothalamus, with distinct patterns between sexes; (6) NPY: In the amygdala, stress reduced Npy and Npy1r levels in males but increased them in females. Alcohol decreased Npy2r levels in males, with varied effects in females. Similar sex-specific patterns were observed in the hypothalamus; (7) Corticoid system: Stress and alcohol had complex, sex-dependent effects on Pomc, Nr3c1, and Nr3c2 in both brain regions; (8) Opioid receptors: Stress and alcohol blunted the elevated expression of Oprm1, Oprd1, and Oprk1 in the amygdala of males and the hypothalamus of females; (8) Vasopressin: Stress and alcohol interacted significantly to affect Avp and Avpr1a expression in the amygdala, with stronger effects in females. In the hypothalamus, alcohol increased Avp levels in females.</p><p><strong>Conclusions: </strong>This study demonstrates that adolescent acute stress and alcohol exposure induce lasting, sex-specific alterations in systems involved in reward and stress responses. These findings emphasize the importance of considering sex differences in the prevention and management of HPA dysfunction and psychiatric disorders.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340542","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":"Application and insights of targeted next-generation sequencing in a large cohort of 46,XY disorders of sex development in Chinese","authors":"Hongyu Chen, Guangjie Chen, Fengxia Li, Yong Huang, Linfeng Zhu, Yijun Zhao, Ziyi Jiang, Xiang Yan, Lan Yu","doi":"10.1186/s13293-024-00648-6","DOIUrl":"https://doi.org/10.1186/s13293-024-00648-6","url":null,"abstract":"46,XY disorders of sex development (46,XY DSD) are characterized by incomplete masculinization of genitalia with reduced androgenization. Accurate clinical management remains challenging, especially based solely on physical examination. Targeted next-generation sequencing (NGS) with known pathogenic genes provides a powerful tool for diagnosis efficiency. This study aims to identify the prevalent genetic variants by targeted NGS technology and investigate the diagnostic rate in a large cohort of 46,XY DSD patients, with most of them presenting atypical phenotypes. Two different DSD panels were developed for sequencing purposes, targeting a cohort of 402 patients diagnosed with 46,XY DSD, who were recruited from the Department of Urology at Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China). The detailed clinical characteristics were evaluated, and peripheral blood was collected for targeted panels to find the patients’ variants. The clinical significance of these variants was annotated according to American College of Medical Genetics and Genomics (ACMG) guidelines. A total of 108 variants across 42 genes were found in 107 patients, including 46 pathogenic or likely pathogenic variants, with 45.7%(21/46) being novel. Among these genes, SRD5A2, AR, FGFR1, LHCGR, NR5A1, CHD7 were the most frequently observed. Besides, we also detected some uncommon causative genes like SOS1, and GNAS. Oligogenic variants were also identified in 9 patients, including several combinations PROKR2/FGFR1/CYP11B1, PROKR2/ATRX, PROKR2/AR, FGFR1/LHCGR/POR, FGFR1/NR5A1, GATA4/NR5A1, WNT4/AR, MAP3K1/FOXL2, WNT4/AR, and SOS1/FOXL2. The overall genetic diagnostic rate was 11.2%(45/402), with an additional 15.4% (62/402) having variants of uncertain significance. Additionally, trio/duo patients had a higher genetic diagnostic rate (13.4%) compared to singletons (8.6%), with a higher proportion of singletons (15.1%) presenting variants of uncertain significance. In conclusion, targeted gene panels identified pathogenic variants in a Chinese 46,XY DSD cohort, expanding the genetic understanding and providing evidence for known pathogenic genes’ involvement. 46,XY disorders of sex development (46,XY DSD) are conditions where individuals don’t fully develop male genitalia due to reduced androgen hormones. Diagnosing these conditions based only on physical exams is difficult. This study used advanced genetic testing called targeted next-generation sequencing (NGS) to identify common genetic variations in a large group of 46,XY DSD patients, many of whom had unusual symptoms. We examined 402 patients with DSD and a 46,XY karyotype, focusing on 142 candidate genes related to sex development. We found genetic variations in 107 patients, including 45 that were likely responsible for their condition. Some of these variations were new discoveries. The most commonly affected genes were SRD5A2, AR, FGFR1, LHCGR, NR5A1, CHD7. We also found that some patients had va","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific molecular signature of mouse podocytes in homeostasis and in response to pharmacological challenge with rapamycin","authors":"Ola Al-Diab, Christin Sünkel, Eric Blanc, Rusan Ali Catar, Muhammad Imtiaz Ashraf, Hongfan Zhao, Pinchao Wang, Markus M. Rinschen, Raphaela Fritsche-Guenther, Florian Grahammer, Sebastian Bachmann, Dieter Beule, Jennifer A. Kirwan, Nikolaus Rajewsky, Tobias B. Huber, Dennis Gürgen, Angelika Kusch","doi":"10.1186/s13293-024-00647-7","DOIUrl":"https://doi.org/10.1186/s13293-024-00647-7","url":null,"abstract":"Sex differences exist in the prevalence and progression of major glomerular diseases. Podocytes are the essential cell-type in the kidney which maintain the physiological blood-urine barrier, and pathological changes in podocyte homeostasis are critical accelerators of impairment of kidney function. However, sex-specific molecular signatures of podocytes under physiological and stress conditions remain unknown. This work aimed at identifying sexual dimorphic molecular signatures of podocytes under physiological condition and pharmacologically challenged homeostasis with mechanistic target of rapamycin (mTOR) inhibition. mTOR is a crucial regulator involved in a variety of physiological and pathological stress responses in the kidney and inhibition of this pathway may therefore serve as a general stress challenger to get fundamental insights into sex differences in podocytes. The genomic ROSAmT/mG-NPHS2 Cre mouse model was used which allows obtaining highly pure podocyte fractions for cell-specific molecular analyses, and vehicle or pharmacologic treatment with the mTOR inhibitor rapamycin was performed for 3 weeks. Subsequently, deep RNA sequencing and proteomics were performed of the isolated podocytes to identify intrinsic sex differences. Studies were supplemented with metabolomics from kidney cortex tissues. Although kidney function and morphology remained normal in all experimental groups, RNA sequencing, proteomics and metabolomics revealed strong intrinsic sex differences in the expression levels of mitochondrial, translation and structural transcripts, protein abundances and regulation of metabolic pathways. Interestingly, rapamycin abolished prominent sex-specific clustering of podocyte gene expression and induced major changes only in male transcriptome. Several sex-biased transcription factors could be identified as possible upstream regulators of these sexually dimorphic responses. Concordant to transcriptomics, metabolomic changes were more prominent in males. Remarkably, high number of previously reported kidney disease genes showed intrinsic sexual dimorphism and/or different response patterns towards mTOR inhibition. Our results highlight remarkable intrinsic sex-differences and sex-specific response patterns towards pharmacological challenged podocyte homeostasis which might fundamentally contribute to sex differences in kidney disease susceptibilities and progression. This work provides rationale and an in-depth database for novel targets to be tested in specific kidney disease models to advance with sex-specific treatment strategies. The global burden of chronic kidney diseases is rapidly increasing and is projected to become the fifth most common cause of years of life lost worldwide by 2040. Sexual dimorphism in kidney diseases and transplantation is well known, yet sex-specific therapeutic strategies are still missing. One reason is the lack of knowledge due to the lack of inclusion of sex as a biological variable in study d","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264193","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":"Correction: MetaFun: unveiling sex-based differences in multiple transcriptomic studies through comprehensive functional meta-analysis","authors":"Pablo Malmierca-Merlo, Rubén Sánchez-Garcia, Rubén Grillo-Risco, Irene Pérez-Díez, José F. Català-Senent, María de la Iglesia-Vayá, Marta R. Hidalgo, Francisco Garcia-Garcia","doi":"10.1186/s13293-024-00646-8","DOIUrl":"https://doi.org/10.1186/s13293-024-00646-8","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction: Biol Sex Differ 15&lt;/b&gt;,&lt;b&gt; 66 (2024)&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/s13293-024-00640-0&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Following publication of the original article [1], the authors reported an error in the funding statement.&lt;/p&gt;&lt;p&gt;The original article [1] has been corrected.&lt;/p&gt;&lt;ol data-track-component=\"outbound reference\" data-track-context=\"references section\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Malmierca-Merlo P, Sánchez-Garcia R, Grillo-Risco R et al. MetaFun: unveiling sex-based differences in multiple transcriptomic studies through comprehensive functional meta-analysis. Biol Sex Differ. 2024;15:66. https://doi.org/10.1186/s13293-024-00640-0&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Computational Biomedicine Laboratory, Principe Felipe Research Center (CIPF), Eduardo Primo Yúfera Street, 3, Valencia, 46012, Spain&lt;/p&gt;&lt;p&gt;Pablo Malmierca-Merlo, Rubén Sánchez-Garcia, Rubén Grillo-Risco, Irene Pérez-Díez, José F. Català-Senent, Marta R. Hidalgo &amp; Francisco Garcia-Garcia&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Biomedical Imaging Unit FISABIOCIPF, Fundación Para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana, Valencia, 46012, Spain&lt;/p&gt;&lt;p&gt;Irene Pérez-Díez &amp; María de la Iglesia-Vayá&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Mathematics, Faculty of Mathematics, University of Valencia (UV), BurjassotValencia, 46100, Spain&lt;/p&gt;&lt;p&gt;Marta R. Hidalgo&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Pablo Malmierca-Merlo&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Rubén Sánchez-Garcia&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Rubén Grillo-Risco&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Irene Pérez-Díez&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;José F. Català-Senent&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;María de la Iglesia-Vayá&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Marta R. Hidalgo&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Francisco Garcia-Garcia&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;h3&gt;Corresponding authors&lt;/h3&gt;&lt;p&gt;Correspondence to Marta R. Hidalgo or Francisco Garcia-Garcia.&lt;/p&gt;&lt;h3&gt;Publisher","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182750","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}