与任何其他科学期刊不同，《性别差异生物学》侧重于生理、行为和疾病方面的性别差异，从分子到表型，并结合了基础和临床研究。该杂志旨在提高对基本原则的理解，并促进针对性别差异的治疗和诊断工具的开发。这本开放获取期刊是性别差异研究组织备受推崇的官方期刊，由女性健康研究协会共同出版。主题领域包括但不限于以下方面的性别差异：基因组学；微生物组；表观遗传学；分子和细胞生物学；组织生物学；生理;任何系统中的组织系统的相互作用，包括脂肪、行为、心血管、免疫、肌肉、神经、肾脏和骨骼；关于疾病性别差异或对治疗反应的临床研究

The journal "Biology of Sex Differences" is a unique scientific publication that focuses on sex differences in physiology, behavior, and disease, spanning from molecular to phenotypic levels, and integrating both basic and clinical research. The journal aims to enhance the understanding of fundamental principles related to sex differences and to promote the development of targeted diagnostic and therapeutic tools. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences, co-published by the Society for Women's Health Research. The thematic areas covered include, but are not limited to, sex differences in genomics, microbiomics, epigenetics, molecular and cellular biology, tissue biology, physiology, and the interactions of organizational systems in various systems, including adipose, behavioral, cardiovascular, immune, muscular, neurological, renal, and skeletal systems; as well as clinical research on disease sex differences or responses to treatment.

《Biology of Sex Differences》是一份独特的科学期刊，专注于生理、行为和疾病方面的性别差异，涵盖从分子到表型的各个层面，并结合基础与临床研究。该期刊旨在加深对性别差异基本原则的理解，并促进针对这些差异的治疗和诊断工具的开发。作为一份开放获取的期刊，它是性别差异研究组织的官方期刊，由女性健康研究协会共同出版。期刊的主题领域包括但不限于以下方面的性别差异：基因组学、微生物组、表观遗传学、分子与细胞生物学、组织生物学、生理学，以及在不同系统中组织系统的相互作用，包括脂肪、行为、心血管、免疫、肌肉、神经、肾脏和骨骼等；同时也涵盖关于疾病性别差异或对治疗反应的临床研究。

Biology of Sex Differences

Young female athletes experience a higher incidence of ligament injuries than their male counterparts, females experience a higher incidence of joint hypermobility syndrome (a risk factor for osteoarthritis development), and post-menopausal females experience a higher prevalence of osteoarthritis than age-matched males. These observations indicate that fluctuating sex hormone levels in young females and loss of ovarian sex hormone production due to menopause likely contribute to observed sex differences in knee joint function and risk for loss of function. In studies of osteoarthritis, however, there is a general lack of appreciation for the heterogeneity of hormonal control in both women and men. Progress in this field is limited by the relatively few preclinical osteoarthritis models, and that most of the work with established models uses only male animals. To elucidate sex differences in osteoarthritis, it is important to examine sex hormone mechanisms in cells from knee tissues and the sexual dimorphism in the role of inflammation at the cell, tissue, and organ levels. There is a need to determine if the risk for loss of knee function and integrity in females is restricted to only the knee or if sex-specific changes in other tissues play a role. This paper discusses these gaps in knowledge and suggests remedies.

Barbara D Boyan

David A Hart

Roger M Enoka

Daniel P Nicolella

Eileen Resnick

Karen J Berkley

Kathleen A Sluka

C Kent Kwoh

Laura L Tosi

Mary I O’Connor

Richard D Coutts

Wendy M Kohrt

Hormonal modulation of connective tissue homeostasis and sex differences in risk for osteoarthritis of the knee

激素对结缔组织稳态的调节及膝关节骨关节炎风险的性别差异

Women have more body fat than men, but in contrast to the deleterious metabolic consequences of the central obesity typical of men, the pear-shaped body fat distribution of many women is associated with lower cardiometabolic risk. To understand the mechanisms regulating adiposity and adipose tissue distribution in men and women, significant research attention has focused on comparing adipocyte morphological and metabolic properties, as well as the capacity of preadipocytes derived from different depots for proliferation and differentiation. Available evidence points to possible intrinsic, cell autonomous differences in preadipocytes and adipocytes, as well as modulatory roles for sex steroids, the microenvironment within each adipose tissue, and developmental factors. Gluteal-femoral adipose tissues of women may simply provide a safe lipid reservoir for excess energy, or they may directly regulate systemic metabolism via release of metabolic products or adipokines. We provide a brief overview of the relationship of fat distribution to metabolic health in men and women, and then focus on mechanisms underlying sex differences in adipose tissue biology.

Kalypso Karastergiou

Steven R Smith

Andrew S Greenberg

Susan K Fried

Sex differences in human adipose tissues – the biology of pear shape

人类脂肪组织的性别差异——梨形身材的生物学

Abstract Obesity is a growing pandemic that increases the risk for cardiovascular diseases, type 2 diabetes, and particularly in women also the risk of cancer and neurodegenerative disorders such as dementia and multiple sclerosis. Preclinical studies on obesity focus on male mice as they gain bodyweight faster and show a clear pro-inflammatory phenotype. Here, using male and female mice, we induced obesity by feeding a high fat diet (HFD), and compared adipose tissue (AT) inflammation at the same adiposity stage (% AT/bodyweight) between both sexes. Doing so, we identified that female mice show an increase in the number of pro-inflammatory immune cells in the visceral AT at a lower adiposity stage than male mice, but the effect of HFD is diminished with higher adiposity. Interestingly, only female mice showed an increase in immune cells in the subcutaneous AT after HFD feeding. Nonetheless, we found that pro-inflammatory cytokines in blood plasma mirror the inflammatory stage of the visceral AT in both male and female mice. Uniquely in male mice, myeloid cells in the visceral AT showed a higher inflammasome activation upon HFD. In summary, we showed that adiposity differentially affects immune cells in fat depots based on sex.

Lisa T. Schuetz

Gayel Duran

Paulien Baeten

Daphne Lintsen

Doryssa Hermans

Sarah Chenine

Janne Verreycken

Tim Vanmierlo

Kristiaan Wouters

Bieke Broux

Sex differentially affects pro-inflammatory cell subsets in adipose tissue depots in a diet induced obesity model

在饮食诱导的肥胖模型中，性别差异性地影响脂肪组织库中的促炎性细胞亚群

Abstract Background Myocarditis is an inflammation of the heart muscle most often caused by viral infections. Sex differences in the immune response during myocarditis have been well described but upstream mechanisms in the heart that might influence sex differences in disease are not completely understood. Methods Male and female BALB/c wild type mice received an intraperitoneal injection of heart-passaged coxsackievirus B3 (CVB3) or vehicle control. Bulk-tissue RNA-sequencing was conducted to better understand sex differences in CVB3 myocarditis. We performed enrichment analysis and functional validation to understand sex differences in the transcriptional landscape of myocarditis and identify factors that might drive sex differences in myocarditis. Results As expected, the hearts of male and female mice with myocarditis were significantly enriched for pathways related to an innate and adaptive immune response compared to uninfected controls. Unique to this study, we found that males were enriched for inflammatory pathways and gene changes that suggested worse mitochondrial electron transport function while females were enriched for pathways related to mitochondrial homeostasis. Mitochondria isolated from the heart of males were confirmed to have worse mitochondrial respiration than females during myocarditis. Unbiased TRANSFAC analysis identified estrogen-related receptor alpha (ERRα) as a transcription factor that may mediate sex differences in mitochondrial function during myocarditis. Transcript and protein levels of ERRα were confirmed as elevated in females with myocarditis compared to males. Differential binding analysis from chromatin immunoprecipitation (ChIP) sequencing confirmed that ERRα bound highly to select predicted respiratory chain genes in females more than males during myocarditis. Conclusions Females with viral myocarditis regulate mitochondrial homeostasis by upregulating master regulators of mitochondrial transcription including ERRα.

Damian N. Di Florio

Gabriel J. Weigel

David J. Gorelov

Elizabeth J. McCabe

Danielle J. Beetler

Katie A. Shapiro

Katelyn A. Bruno

Isha Chekuri

Angita Jain

Emily R. Whelan

Gary R. Salomon

Sami Khatib

Natalie E. Bonvie-Hill

Jessica J. Fliess

Presley G. Giresi

Charwan Hamilton

Cameron J. Hartmoyer

Varsini Balamurugan

Ashley A. Darakjian

Brandy H. Edenfield

S. Christian Kocsis

Christopher J. McLeod

Leslie T. Cooper

Étienne Audet-Walsh

Michael J. Coronado

Jon Sin

DeLisa Fairweather

Sex differences in mitochondrial gene expression during viral myocarditis

病毒性心肌炎中线粒体基因表达的性别差异

Abstract Background DNA methylation (DNAm) influences both sex differences and cancer development, yet the mechanisms connecting these factors remain unclear. Methods Utilizing data from The Cancer Genome Atlas, we conducted a comprehensive analysis of sex-related DNAm effects in nine non-reproductive cancers, compared to paired normal adjacent tissues (NATs), and validated the results using independent datasets. First, we assessed the extent of sex differential DNAm between cancers and NATs to explore how sex-related DNAm differences change in cancerous tissues. Next, we employed a multivariate adaptive shrinkage approach to model the covariance of cancer-related DNAm effects between sexes, aiming to elucidate how sex impacts aberrant DNAm patterns in cancers. Finally, we investigated correlations between the methylome and transcriptome to identify key signals driving sex-biased DNAm regulation in cancers. Results Our analysis revealed a significant attenuation of sex differences in DNAm within cancerous tissues compared to baseline differences in normal tissues. We identified 3,452 CpGs ( P bonf &lt; 0.05) associated with this reduction, with 72% of the linked genes involved in X chromosome inactivation. Through covariance analysis, we demonstrated that sex differences in cancer are predominantly driven by variations in the magnitude of shared DNAm signals, referred to as “amplification.” Based on these patterns, we classified cancers into female- and male-biased groups and identified key CpGs exhibiting sex-specific amplification. These CpGs were enriched in binding sites of critical transcription factors, including P53, SOX2, and CTCF. Integrative multi-omics analyses uncovered 48 CpG-gene-cancer trios for females and 380 for males, showing similar magnitude differences in DNAm and gene expression, pointing to a sex-specific regulatory role of DNAm in cancer risk. Notably, several genes regulated by these trios were previously identified as drug targets for cancers, highlighting their potential as sex-specific therapeutic targets. Conclusions These findings advance our understanding of how sex, DNAm, and gene expression interact in cancer, offering insights into the development of sex-specific biomarkers and precision medicine.

Jiaqi Zhou

Miao Li

Yu Chen

Shangzi Wang

Danke Wang

Chen Suo

Xingdong Chen

Attenuated sex-related DNA methylation differences in cancer highlight the magnitude bias mediating existing disparities

癌症中性别相关DNA甲基化差异的减弱突显了介导现有差异的幅度偏差

Abstract Background Women have a higher risk of developing osteoarthritis (OA) than men, including with obesity. To better understand this disparity, we investigated sex differences in metabolic and inflammatory factors associated with OA using a diet-induced mouse model of obesity. We hypothesized that 20 weeks of high-fat diet (HFD) would induce sexually dimorphic changes in both systemic and local risk factors of knee OA. Methods Male and female C57BL/6J mice were fed Chow or HFD from 6 to 26 weeks of age ( n = 12 per diet and sex). We performed broad metabolic phenotyping, 16 S gut microbiome analysis, targeted gene expression analysis of synovium-infrapatellar fat tissue, targeted gene expression and proteomic analysis of articular cartilage, chondrocyte metabolic profiling, and OA histopathology. Two-way ANOVA statistics were utilized to determine the contribution of sex and diet and their interaction on outcomes. Results Mice fed HFD weighed 1.76-fold ( p &lt; 0.0001) and 1.60-fold ( p &lt; 0.0001) more than male and female Chow cohorts, respectively, with both sexes reaching similar body fat levels (male: 43.9 ± 2.2%; female: 44.1 ± 3.8%). HFD caused greater cartilage pathology ( p &lt; 0.024) and synovial hyperplasia ( p &lt; 0.038) versus Chow in both sexes. Cartilage pathology was greater in male versus female mice ( p = 0.048), and only male mice developed osteophytes with HFD ( p = 0.044). Both sexes exhibited metabolic inflexibility on HFD, but only male mice developed glucose intolerance ( p &lt; 0.0001), fatty liver ( p &lt; 0.0001), and elevated serum amylase ( p &lt; 0.0001) with HFD versus Chow. HFD treatment caused sex-dependent differences in gut microbiota beta diversity ( p = 0.01) and alteration in specific microbiome clades, such as a HFD-dependent reduction in abundance of Bifidobacterium only in male mice. In knee synovium and infrapatellar fat tissue, HFD upregulated the expression of pro-inflammatory and pro-fibrotic genes predominantly in female mice. In cartilage, lipid metabolism proteins were more abundant with HFD in male mice, whereas proteins involved in glycolysis/gluconeogenesis and biosynthesis of amino acids were greater in cartilage of female mice. Sex-dependent metabolic differences were observed in cartilage from young, healthy mice prior to pubertal maturation, but not in primary juvenile chondrocytes studied in vitro. Conclusions HFD induced numerous sex differences in metabolic and inflammatory outcomes, especially in joint tissues, suggesting that sex-specific cellular processes are involved during development of early-stage OA with obesity.

Timothy M. Griffin

Erika Barboza Prado Lopes

Dominic Cortassa

Albert Batushansky

Matlock A. Jeffries

Dawid Makosa

Anita Jopkiewicz

Padmaja Mehta-D’souza

Ravi K. Komaravolu

Michael T. Kinter

Sexually dimorphic metabolic effects of a high fat diet on knee osteoarthritis in mice

高脂饮食对小鼠膝关节骨关节炎的性别二态性代谢影响

Abstract Background The circadian clock integrates external environmental changes into the internal physiology of organisms. Perturbed circadian clocks due to misaligned light cycles increase the risk of diseases, including metabolic disorders. However, the effects of sex differences in this context remain unclear. Methods Circadian misalignment was induced by a chronic jet lag (CJL) shift schedule (light-on time advanced by 6 h every 2 days) in C57BL/6N male and female mice. Core body temperature and activity rhythms were recorded using a nano tag, and the gene expression rhythms of clock and clock-controlled genes in the liver and adrenal glands were analyzed using qPCR. Glucose metabolism and insulin response were evaluated using glucose tolerance, insulin sensitivity, and glucose response assays. Castration and testosterone replacement were performed to assess the fundamental role of testosterone in male phenotypes under CJL. Results Under CJL treatment, male mice exhibited increased weight gain, whereas females exhibited decreased weight gain compared to that of the respective controls. CJL treatment induced a lower robustness of circadian rhythms in core body temperature and a weaker rhythm of clock gene expression in the liver and adrenal glands in females, but not in males. Only male mice exhibited glucose intolerance under CJL conditions, without the development of insulin resistance. Castrated mice without testosterone exhibited decreased weight gain and reduced robustness of body temperature rhythm, as observed in intact females. Testosterone replacement in castrated mice recovered the CJL-induced weight gain, robustness of temperature rhythm, and glucose intolerance observed in intact males. Conclusions Significant sex-based differences were observed in circadian clock organization and metabolism under CJL. Testosterone plays a crucial role in maintaining the circadian clock and regulating CJL metabolism in males.

Tiantian Ma

Ryohei Matsuo

Kaito Kurogi

Shunsuke Miyamoto

Tatsumi Morita

Marina Shinozuka

Fuka Taniguchi

Keisuke Ikegami

Shinobu Yasuo

Sex-dependent effects of chronic jet lag on circadian rhythm and metabolism in mice

慢性时差对小鼠昼夜节律和代谢的性别依赖性影响

Abbreviation	Biol. Sex Differ.
Journal Impact	4.82
Quartiles(Global)	GENETICS & HEREDITY(Q1)

ISSN	2042-6410
h-index	61

Publication Information	Publisher: BioMed Central Ltd，Publishing cycle: ，Journal Type: journal，Open Access Journals: Yes
Basic data	Year of publication: 2010，Proportion of original research papers: 83.56%，Self Citation Rate:2.00%， Gold OA Rate: 99.55%
Journal Fees	$3190Details
Average review cycle	网友分享经验：14 Weeks

Biology of Sex Differences

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Hormonal modulation of connective tissue homeostasis and sex differences in risk for osteoarthritis of the knee

Sex differences in human adipose tissues – the biology of pear shape

Sex differentially affects pro-inflammatory cell subsets in adipose tissue depots in a diet induced obesity model

Sex differences in mitochondrial gene expression during viral myocarditis

Attenuated sex-related DNA methylation differences in cancer highlight the magnitude bias mediating existing disparities

Attenuated sex-related DNA methylation differences in cancer highlight the magnitude bias mediating existing disparities

Sex differentially affects pro-inflammatory cell subsets in adipose tissue depots in a diet induced obesity model

Sex differences in mitochondrial gene expression during viral myocarditis

Sexually dimorphic metabolic effects of a high fat diet on knee osteoarthritis in mice

Sex-dependent effects of chronic jet lag on circadian rhythm and metabolism in mice