Biology of Sex Differences最新文献

{"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}

{"title":"Sex differences in sleep deficits in mice with an autism-linked Shank3 mutation.","authors":"Elizabeth Medina, Michael J Rempe, Christine Muheim, Hannah Schoch, Kristan Singletary, Kaitlyn Ford, Lucia Peixoto","doi":"10.1186/s13293-024-00664-6","DOIUrl":"10.1186/s13293-024-00664-6","url":null,"abstract":"<p><strong>Background: </strong>Insomnia is more prevalent in individuals with Autism Spectrum Disorder (ASD), can worsen core-symptoms and reduces quality of life of both individuals and caregivers. Although ASD is four times more prevalent in males than females, less is known about sex specific sleep differences in autistic individuals. Recent ASD studies suggest that sleep problems may be more severe in females, which aligns with the sex bias seen in insomnia for the general population. We have previously shown that male mice with a mutation in the high confidence ASD gene Shank3, Shank3^∆C, recapitulate most aspects of the ASD insomnia phenotype. The objective of the present study was to leverage the Shank3^∆C model to investigate sex-specific effects in sleep using polysomnography.</p><p><strong>Methods: </strong>Adult male and female Shank3^∆C and wildtype (WT) littermates were first recorded for 24 h of baseline recordings. Subsequently, they were sleep deprived (SD) for five hours via gentle handling and allowed 19 h of recovery sleep to characterize the homeostatic response to SD. Vigilance states (rapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep and wake) were assigned by manual inspection using SleepSign. Data processing, statistical analysis and visualization were conducted using MATLAB.</p><p><strong>Results: </strong>Sex and genotype effects were found during baseline sleep and after SD. At baseline, male Shank3^∆C mice sleep less during the dark period (active phase) while female Shank3^∆C mice sleep less during the light period (rest phase) and sleep more during the dark period. Both male and female Shank3^∆C mice show reduced spectral power in NREM sleep. We detect a significant effect of sex and genotype in sleep onset latency and homeostatic sleep pressure (sleepiness). In addition, while male Shank3^∆C mice fail to increase sleep time following SD as seen in WT, female Shank3^∆C mice decrease sleep time.</p><p><strong>Conclusions: </strong>Overall, our study demonstrates sex differences in sleep architecture and homeostatic response to SD in adult Shank3^∆C mice. Thus, our study demonstrates an interaction between sex and genotype in Shank3^∆C mice and supports the use of the Shank3^∆C model to better understand mechanisms contributing to the sex differences in insomnia in ASD in clinical populations.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"85"},"PeriodicalIF":4.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520901","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":"Age, sex, and cell type-resolved hypothalamic gene expression across the pubertal transition in mice.","authors":"Dustin J Sokolowski, Huayun Hou, Kyoko E Yuki, Anna Roy, Cadia Chan, Wendy Choi, Mariela Faykoo-Martinez, Matt Hudson, Christina Corre, Liis Uusküla-Reimand, Anna Goldenberg, Mark R Palmert, Michael D Wilson","doi":"10.1186/s13293-024-00661-9","DOIUrl":"10.1186/s13293-024-00661-9","url":null,"abstract":"<p><strong>Background: </strong>The hypothalamus plays a central role in regulating puberty. However, our knowledge of the postnatal gene regulatory networks that control the pubertal transition in males and females is incomplete. Here, we investigate the age-, sex- and cell-type-specific gene regulation in the hypothalamus across the pubertal transition.</p><p><strong>Methods: </strong>We used RNA-seq to profile hypothalamic gene expression in male and female mice at five time points spanning the onset of puberty (postnatal days (PD) 12, 22, 27, 32, and 37). By combining this data with hypothalamic single nuclei RNA-seq data from pre- and postpubertal mice, we assigned gene expression changes to their most likely cell types of origin. In our colony, pubertal onset occurs earlier in male mice, allowing us to focus on genes whose expression is dynamic across ages and offset between sexes, and to explore the bases of sex effects.</p><p><strong>Results: </strong>Our age-by-sex pattern of expression enriched for biological pathways involved hormone production, neuronal activation, and glial maturation. Additionally, we inferred a robust expansion of oligodendrocytes precursor cells into mature oligodendrocytes spanning the prepubertal (PD12) to peri-pubertal (PD27) timepoints. Using spatial transcriptomic data from postpubertal mice, we observed the lateral hypothalamic area and zona incerta were the most oligodendrocyte-rich regions and that these cells expressed genes known to be involved in pubertal regulation.</p><p><strong>Conclusion: </strong>Together, by incorporating multiple biological timepoints and using sex as a variable, we identified gene and cell-type changes that may participate in orchestrating the pubertal transition and provided a resource for future studies of postnatal hypothalamic gene regulation.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"83"},"PeriodicalIF":4.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494069","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":"Aromatase, testosterone, TMPRSS2: determinants of COVID-19 severity.","authors":"Eric C Mohan, Jude P J Savarraj, Gabriela D Colpo, Diego Morales, Carson E Finger, Alexis McAlister, Hilda Ahnstedt, HuiMahn Choi, Louise D McCullough, Bharti Manwani","doi":"10.1186/s13293-024-00658-4","DOIUrl":"10.1186/s13293-024-00658-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Male sex has been identified as a risk factor for worse COVID-19 outcomes. This sex difference has been mostly attributed to the complex role of sex hormones. Cell surface entry of SARS-CoV-2 is mediated by the transmembrane protease serine 2 (TMPRSS2) which is under transcriptional regulation by androgens. P450 aromatase enzyme converts androgens to estrogens. This study measured concentrations of aromatase enzyme, testosterone, estradiol, and TMPRSS-2 in plasma of hospitalized COVID-19 patients to elucidate the dynamics of sex-linked disparity in COVID-19 and correlate them with disease severity and mortality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this prospective cohort study, a total of 265 patients (41% women), age 18 years and older, who had a positive COVID-19 PCR test and were hospitalized for COVID-19 at Memorial Hermann Hospital in Houston, (between May 2020 and May 2021) were enrolled in the study if met inclusion criteria. Plasma concentrations of Testosterone, aromatase, TMPRSS-2, and estradiol were measured by ELISA. COVID-19 patients were dichotomized based on disease severity into moderate-severe (n = 146) or critical (n = 119). Mann Whitney U and logistic regression were used to correlate the analytes with disease severity and mortality.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;TMPRSS2 (2.5 ± 0.31 vs. 1.73 ± 0.21 ng/mL, p &lt; 0.01) and testosterone (1.2 ± 0.1 vs. 0.44 ± 0.12 ng/mL, p &lt; 0.01) were significantly higher in men as compared to women with COVID-19 after adjusting for age in a multivariate model. There was no sex difference seen in the level of estradiol and aromatase in COVID-19 patients. TMPRSS2 and aromatase were higher, while testosterone was lower in patients with increased COVID-19 severity. They were independently associated with COVID-19 severity, after adjusting for several baseline risk factors in a multivariate logistic regression model. In terms of mortality, TMPRRS2 and aromatase levels were significantly higher in non-survivors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Our study demonstrates that testosterone, aromatase, and TMPRSS2 are markers of COVID-19 severity. Estradiol levels do not change with disease severity in COVID-19. In terms of mortality prediction, higher aromatase and TMPRSS-2 levels can be used to predict mortality from COVID-19 in hospitalized patients. COVID-19 has caused over a million deaths in the U.S., with men often getting sicker than women. Testosterone, a male hormone, helps control a protein called TMPRSS-2, which allows the COVID-19 virus to spread more easily in the body. A protein called aromatase converts the male hormone testosterone into the female hormone estrogen. It is thought that female hormone estrogen helps protect women from getting seriously ill from COVID-19. To understand the role of these hormones in COVID-19 and sex differences, we measured levels of testosterone, estrogen, aromatase (which turns testosterone into estrogen), and TMPRSS-2 in hospi","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"84"},"PeriodicalIF":4.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494070","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}