Biology of Sex Differences最新文献

{"title":"3D in vitro modelling of post-partum cardiovascular health reveals unique characteristics and signatures following hypertensive disorders in pregnancy.","authors":"Clara Liu Chung Ming, Dillan Pienaar, Sahar Ghorbanpour, Hao Chen, Lynne Margaret Roberts, Louise Cole, Kristine C McGrath, Matthew P Padula, Amanda Henry, Carmine Gentile, Lana McClements","doi":"10.1186/s13293-024-00672-6","DOIUrl":"10.1186/s13293-024-00672-6","url":null,"abstract":"<p><strong>Background: </strong>Hypertensive disorders of pregnancy (HDP) affect 2-8% of pregnancies and are associated postpartum with increased cardiovascular disease (CVD) risk, although mechanisms are poorly understood.</p><p><strong>Methods: </strong>Human induced pluripotent stem cells (iPSC)-derived cardiomyocytes, cardiac fibroblasts and coronary artery endothelial cells were cocultured to form cardiac spheroids (CSs) in collagen type-1 hydrogels containing 10% patient plasma collected five years postpartum [n = 5 per group: normotensive control, gestational hypertension (GH) and preeclampsia (PE)]. Plasma-treated CSs were assessed for cell viability and contractile function and subjected to immunofluorescence staining and imaging. A quantitative proteomic analysis of plasma samples was conducted (controls n = 21; GH n = 5; PE n = 12).</p><p><strong>Results: </strong>Contraction frequency (CF) was increased in PE-treated CSs (CF: 45.5 ± 3.4 contractions/minute, p < 0.001) and GH-treated CSs (CF: 45.7 ± 4.0 contractions/minute, p < 0.001), compared to controls (CF = 21.8 ± 2.6 contractions/min). Only PE-treated CSs presented significantly increased fractional shortening (FS) % (9.95 ± 1.8%, p < 0.05) compared to controls (3.7 ± 1.1%). GH-treated CSs showed a reduction in cell viability (p < 0.05) and an increase in α-SMA expression (p < 0.05). Proteomics analyses identified twenty differentially abundant proteins, with hemoglobin A2 being the only protein perturbed in both GH and PE versus control plasma (p < 0.05).</p><p><strong>Conclusions: </strong>The innovative patient-relevant CS platforms led to the discovery of biomarkers/targets linked to cell death signaling and cardiac remodeling in GH-induced CVD and vascular/endothelial cell dysfunction in PE-induced CVD.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"94"},"PeriodicalIF":4.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715250","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":"Reconsidering tools for measuring gender dimensions in biomedical research.","authors":"Rosemary Morgan, Anna Yin, Anna Kalbarczyk, Janna R Shapiro, Patrick J Shea, Helen Kuo, Carmen H Rodriguez, Erica N Rosser, Andrew Pekosz, Sean X Leng, Sabra L Klein","doi":"10.1186/s13293-024-00663-7","DOIUrl":"10.1186/s13293-024-00663-7","url":null,"abstract":"<p><p>Sex and gender play important roles in contributing to disease and health outcomes and represent essential, but often overlooked, measures in biomedical research. The context-specific, multifaceted, and relational nature of gender norms, roles, and relations (i.e., gender dimensions) make their incorporation into biomedical research challenging. Gender scores-measures of gender dimensions-can help researchers incorporate gender into quantitative methodologies. These measures enable researchers to quantify the gendered dimensions of interest using data collected from survey respondents. To highlight the complexities of using gender scores within biomedical research, we used the application of the Bem Sex Role Inventory (BSRI) scale, a commonly used gender score, to explore gender differences in adverse events to the influenza vaccine among older adults (75+). Within this paper, we focus on the findings from our longitudinal gender score data collected over three influenza seasons (2019-20, 2020-21, and 2021-22), irrespective of adverse event data, to provide commentary on the reliability of gender scores, such as the BSRI, and the complexities of their application. Of the 162 total study participants included within the study, 69 were enrolled in all three consecutive seasons and 35 participants were enrolled in two consecutive seasons. The majority of participants had a different gender score in at least one of the years, demonstrating the nuances and fluidity of gender identity. Interpretations of BSRI data (or other gender score data) when measured against outcome data must, therefore, be time and context specific, as results are unlikely to be replicated across years.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"96"},"PeriodicalIF":4.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715199","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 role of AKAP12 in behavioral function of middle-aged mice.","authors":"Hidehiro Ishikawa, Shintaro Kimura, Hajime Takase, Maximillian Borlongan, Norito Fukuda, Tomonori Hoshino, Gen Hamanaka, Ji Hyun Park, Akihiro Shindo, Kyu-Won Kim, Irwin H Gelman, Josephine Lok, Eng H Lo, Ken Arai","doi":"10.1186/s13293-024-00670-8","DOIUrl":"10.1186/s13293-024-00670-8","url":null,"abstract":"<p><p>A-kinase anchoring protein 12 (AKAP12) is a key scaffolding protein that regulates cellular signaling by anchoring protein kinase A (PKA) and other signaling molecules. While recent studies suggest an important role for AKAP12 in the brain, including cognitive functions, its role in middle-aged mice and potential sex differences are not fully understood. Therefore, this study investigated the effects of AKAP12 on cognitive and exploratory behavior in middle-aged mice, focusing on sex differences. Cognitive function was assessed using the spontaneous Y-maze test and the novel object recognition test (NORT). No significant sex differences in cognitive function were found in middle-aged C57BL/6J mice; however, female mice showed greater exploratory behavior during the NORT. In addition, both middle-aged male and female Akap12 knockout (KO) mice performed similarly to wild-type (WT) mice in the Y-maze test, but had lower discrimination indices in the NORT, suggesting a potential role for AKAP12 in short-term memory. Notably, exploratory behavior was suppressed in female Akap12 KO mice compared to WT mice, whereas male Akap12 KO mice did not show this effect. There were no significant differences in movement distance and velocity during the Y-maze test and NORT between WT and KO mice of either sex. These results indicate that AKAP12 affects cognitive function and exploratory behavior in middle-aged mice and that these effects differ between sexes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"93"},"PeriodicalIF":4.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685855","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 human brain related to visual motion perception.","authors":"Dong-Yu Liu, Ming Li, Juan Yu, Yuan Gao, Xiaotong Zhang, Dewen Hu, Georg Northoff, Xue Mei Song, Junming Zhu","doi":"10.1186/s13293-024-00668-2","DOIUrl":"10.1186/s13293-024-00668-2","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have found that the temporal duration required for males to perceive visual motion direction is significantly shorter than that for females. However, the neural correlates of such shortened duration perception remain yet unclear. Given that motion perception is primarily associated with the neural activity of the middle temporal visual complex (MT+), we here test the novel hypothesis that the neural mechanism of these behavioral sex differences is mainly related to the MT+ region.</p><p><strong>Methods: </strong>We utilized ultra-high field (UHF) MRI to investigate sex differences in the MT+ brain region. A total of 95 subjects (48 females) participated in two separate studies. Cohort 1, consisting of 33 subjects (16 females), completed task-fMRI (drafting grating stimuli) experiment. Cohort 2, comprising 62 subjects (32 females), engaged in a psychophysical experiment measuring motion perception along different temporal thresholds as well as conducting structural and functional MRI scanning of MT+.</p><p><strong>Results: </strong>Our findings show pronounced sex differences in major brain parameters within the left MT+ (but not the right MT+, i.e., laterality). In particular, males demonstrate (i) larger gray matter volume (GMV) and higher brain's spontaneous activity at the fastest infra-slow frequency band in the left MT+; and (ii) stronger functional connectivity between the left MT+ and the left centromedial amygdala (CM). Meanwhile, both female and male participants exhibited comparable correlations between motion perception ability and the multimodal imaging indexes of the MT+ region, i.e., larger GMV, higher brain's spontaneous activity, and faster motion discrimination.</p><p><strong>Conclusions: </strong>Our findings reveal sex differences of imaging indicators of structure and function in the MT+ region, which also relate to the temporal threshold of motion discrimination. Overall, these results show how behavioral sex differences in visual motion perception are generated, and advocate considering sex as a crucial biological variable in both human brain and behavioral research.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"92"},"PeriodicalIF":4.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635858","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":"A call for inclusive research, policies, and leadership to close the global women's health gap.","authors":"Irene O Aninye","doi":"10.1186/s13293-024-00669-1","DOIUrl":"10.1186/s13293-024-00669-1","url":null,"abstract":"<p><p>Women comprise approximately half of the world's population, yet they are often underrepresented and inadequately considered in medical and public health research and in health care delivery in the United States and around the world. Elucidating sex and gender differences in disease and fundamental hormonal drivers of women's health is instrumental to informing our overall understanding of human health and improving women's health outcomes across the lifespan. The Society for Women's Health Research and ECH Alliance-The Global Health Connector hosted a women's health program as part of the United Nations 79th General Assembly Science Summit. Here, I briefly describe the basis for this convening to address global gender health gaps and reflect on the event's presentations and discussions to recognize and better integrate women's unique health needs in the sustainable development goals.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"91"},"PeriodicalIF":4.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614157","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 Four Core Genotypes mouse model: evaluating the impact of a recently discovered translocation.","authors":"Carrie B Wiese, Barbara Soliman, Karen Reue","doi":"10.1186/s13293-024-00665-5","DOIUrl":"10.1186/s13293-024-00665-5","url":null,"abstract":"<p><p>The Four Core Genotypes (FCG) mouse model has become a valuable model to study the mechanistic basis for biological sex differences. This model allows discrimination between influences of gonadal sex (ovaries or testes) from those associated with genetic sex (presence of XX or XY chromosome complement). FCG mice have illuminated distinct effects of gonadal and chromosomal sex on traits ranging from brain structure and behavior to vulnerability to obesity, atherosclerosis, multiple sclerosis, Alzheimer's and other diseases. A recent study determined that the Y^Sry- chromosome used in a specific line of C57BL/6J FCG mice harbors nine genes that have been duplicated from the X chromosome. This report raised concern that scores of publications that previously used the FCG model may therefore be flawed, but did not provide details regarding how studies can be evaluated for potential impact (or lack of impact) of the translocation. Here we (1) provide a practical description of the genetic translocation for researchers using the FCG model, (2) document that a majority of the studies cited in the recent report are unlikely to be affected by the translocation, (3) provide a scheme for interpreting data from studies with FCG mice harboring the Y^Sry- translocation, and (4) delineate expression levels of the nine translocated genes across tissue/cell types as a filter for evaluating their potential involvement in specific phenotypes.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"90"},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557076","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 contextual fear conditioning and extinction after acute and chronic nicotine treatment.","authors":"Jack V Keady, Marissa C Hessing, Judy C Songrady, Kristen McLaurin, Jill R Turner","doi":"10.1186/s13293-024-00656-6","DOIUrl":"10.1186/s13293-024-00656-6","url":null,"abstract":"<p><strong>Background: </strong>Chronic cigarette smokers report withdrawal symptomology, including affective dysfunction and cognitive deficits. While there are studies demonstrating sex specific withdrawal symptomology in nicotine-dependent individuals, literature examining the underlying biological mediators of this is scant and not in complete agreement. Therefore, in this study, we evaluated the sex specific effects of nicotine and withdrawal on contextual fear memory, a hippocampally dependent aspect of cognition that is disrupted in nicotine withdrawal.</p><p><strong>Methods: </strong>Male and female B6/129F1 mice (8-13 weeks old) were used in all experiments. For the acute nicotine experiment, mice received intraperitoneal saline or nicotine (0.5 mg/kg) prior to contextual fear conditioning and test. For the chronic nicotine experiment, mice received nicotine (18 mg/kg/day) or saline for 11 days, then underwent contextual fear conditioning and test. Following the test, mice underwent minipump removal to elicit withdrawal or sham surgery, followed by the fear extinction assay. Bulk cortical tissue was used to determine nicotinic acetylcholine receptor levels via single point [³H]Epibatidine binding assay. Gene expression levels in the dorsal and ventral hippocampus were quantified via RT-PCR.</p><p><strong>Results: </strong>We found that female mice had a stronger expression of contextual fear memory than their male counterparts. Further, following acute nicotine treatment, male, but not female, subjects demonstrated augmented contextual fear memory expression. In contrast, no significant effects of chronic nicotine treatment on fear conditioning were observed in either sex. When examining extinction of fear learning, we observed that female mice withdrawn from nicotine displayed impaired extinction learning, but no effect was observed in males. Nicotine withdrawal caused similar suppression of fosb, cfos, and bdnf, our proxy for neuronal activation and plasticity changes, in the dorsal and ventral hippocampus of both sexes. Additionally, we found that ventral hippocampus erbb4 expression, a gene implicated in smoking cessation outcomes, was elevated in both sexes following nicotine withdrawal.</p><p><strong>Conclusions: </strong>Despite the similar impacts of nicotine withdrawal on gene expression levels, fosb, cfos, bdnf and erbb4 levels in the ventral hippocampus were predictive of delays in female extinction learning alone. This suggests sex specific dysfunction in hippocampal circuitry may contribute to female specific nicotine withdrawal induced deficits in extinction learning.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"88"},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557074","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 dimorphism and tissue specificity of gene expression changes in aging mice.","authors":"Dantong Zhu, Matt Arnold, Brady A Samuelson, Judy Z Wu, Amber Mueller, David A Sinclair, Alice E Kane","doi":"10.1186/s13293-024-00666-4","DOIUrl":"10.1186/s13293-024-00666-4","url":null,"abstract":"<p><strong>Background: </strong>Aging is a complex process that involves all tissues in an organism and shows sex dimorphism. While transcriptional changes in aging have been well characterized, the majority of studies have focused on a single sex and sex differences in gene expression in aging are poorly understood. In this study, we explore sex dimorphism in gene expression in aging mice across three tissues.</p><p><strong>Methods: </strong>We collected gastrocnemius muscle, liver and white adipose tissue from young (6 months, n = 14) and old (24 months, n = 14) female and male C57BL/6NIA mice and performed RNA-seq. To investigate sex dimorphism in aging, we considered two levels of comparisons: (a) differentially expressed genes between females and males in the old age group and (b) comparisons between females and males across the aging process. We utilized differential expression analysis and gene feature selection to investigate candidate genes. Gene set enrichment analysis was performed to identify candidate molecular pathways. Furthermore, we performed a co-expression network analysis and chose the gene module(s) associated with aging independent of sex or tissue-type.</p><p><strong>Results: </strong>We identified both tissue-specific and tissue-independent genes associated with sex dimorphism in aged mice. Unique differentially expressed genes between old males and females across tissues were mainly enriched for pathways related to specific tissue function. We found similar results when exploring sex differences in the aging process, with the exception that in the liver genes enriched for lipid metabolism and digestive system were identified in both females and males. Combining enriched pathways across analyses, we identified amino acid metabolism, digestive system, and lipid metabolism as the core mechanisms of sex dimorphism in aging. Although the vast majority of age-related genes were sex and tissue specific, we identified 127 hub genes contributing to aging independent of sex and tissue that were enriched for the immune system and signal transduction.</p><p><strong>Conclusions: </strong>There are clear sex differences in gene expression in aging across liver, muscle and white adipose. Core pathways, including amino acid metabolism, digestive system and lipid metabolism, contribute to sex differences in aging.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"89"},"PeriodicalIF":4.9,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557075","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":"Quantitative proteomic profiling reveals sexual dimorphism in the retina and RPE of C57BL6 mice.","authors":"Geeng-Fu Jang, John S Crabb, Allison Grenell, Alyson Wolk, Christie Campla, Shiming Luo, Mariya Ali, Bo Hu, Belinda Willard, Bela Anand-Apte","doi":"10.1186/s13293-024-00645-9","DOIUrl":"10.1186/s13293-024-00645-9","url":null,"abstract":"<p><strong>Background: </strong>Sex as a biological variable is not a common consideration in molecular mechanistic or preclinical studies of retinal diseases. Understanding the sexual dimorphism of adult RPE and retina under physiological conditions is an important first step in improving our understanding of sex-based physio-pathological mechanisms.</p><p><strong>Methods: </strong>Isobaric tags for relative and absolute quantitation (iTRAQ) were used for quantitative proteomics of male and female mouse retina and RPE (10 mice of each sex for each tissue type). Differentially expressed proteins were subjected to Gene Ontology (GO) analysis and Ingenuity Pathway Analysis (IPA).</p><p><strong>Results: </strong>Differential expression analysis identified 21 differentially expressed proteins in the retina and 58 differentially expressed proteins in the RPE. Ingenuity pathway analysis identified the top canonical pathways differentially activated in the retina to be calcium transport I, nucleotide excision repair, molecular transport and cell death and survival. In the RPE, the top canonical pathways were calcium signaling, dilated cardiomyopathy signaling, actin cytoskeletal signaling and cellular assembly and organization.</p><p><strong>Conclusions: </strong>These results provide insights into sex differences in the retina and RPE proteome of mice and begin to shed clues into the sexual dimorphism seen in retinal diseases.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"87"},"PeriodicalIF":4.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543418","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":"Human-specific protein-coding and lncRNA genes cast sex-biased genes in the brain and their relationships with brain diseases.","authors":"Sha He, Xuecong Zhang, Hao Zhu","doi":"10.1186/s13293-024-00659-3","DOIUrl":"10.1186/s13293-024-00659-3","url":null,"abstract":"<p><strong>Background: </strong>Gene expression shows sex bias in the brain as it does in other organs. Since female and male humans exhibit noticeable differences in emotions, logical thinking, movement, spatial orientation, and even the incidence of neurological disorders, sex biases in the brain are especially interesting, but how they are determined, whether they are conserved or lineage specific, and what the consequences of the biases are, remain poorly explored and understood.</p><p><strong>Methods: </strong>Based on RNA-seq datasets from 16  and 14 brain regions in humans and macaques across developmental periods and from patients with brain diseases, we used linear mixed models (LMMs) to differentiate variations in gene expression caused by factors of interest and confounding factors and identify four types of sex-biased genes. Effect size and confidence in each effect were measured upon the local false sign rate (LFSR). We utilized the biomaRt R package to acquire orthologous genes in humans and macaques from the BioMart Ensembl website. Transcriptional regulation of sex-biased genes by sex hormones and lncRNAs were analyzed using the CellOracle, GENIE3, and Longtarget programs. Sex-biased genes' functions were revealed by gene set enrichment analysis using multiple methods.</p><p><strong>Results: </strong>Lineage-specific sex-biased genes greatly determine the distinct sex biases in human and macaque brains. In humans, those encoding proteins contribute directly to immune-related functions, and those encoding lncRNAs intensively regulate the expression of other sex-biased genes, especially genes with immune-related functions. The identified sex-specific differentially expressed genes (ssDEGs) upon gene expression in disease and normal samples also indicate that protein-coding ssDEGs are conserved in humans and macaques but that lncRNA ssDEGs are not conserved. The results answer the above questions, reveal an intrinsic relationship between sex biases in the brain and sex-biased susceptibility to brain diseases, and will help researchers investigate human- and sex-specific ncRNA targets for brain diseases.</p><p><strong>Conclusions: </strong>Human-specific genes greatly cast sex-biased genes in the brain and their relationships with brain diseases, with protein-coding genes contributing to immune response related functions and lncRNA genes critically regulating sex-biased genes. The high proportions of lineage-specific lncRNAs in mammalian genomes indicate that sex biases may have evolved rapidly in not only the brain but also other organs.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"86"},"PeriodicalIF":4.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543417","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}