Biology of Sex Differences最新文献

Objectives: A scoping review was conducted to investigate knowledge gaps in the informatics research literature regarding sex differences in cognitive decline and impairment, identifying existing studies and areas requiring further exploration.

Methods and materials: Our scoping review follows the Preferred Reporting Items for Systematic reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA - ScR) guidelines. We searched Ovid and other databases (APA PsychInfo, EMB Reviews, and Embase) for studies on sex differences in cognitive decline and impairment, focusing on peer-reviewed informatics journals and conference proceedings from 2000 to 2025. The selected manuscripts were analyzed based on metadata statistics, study attributes, and thematic content.

Results: A total of 17 full articles met the inclusion criteria. Most studies were conducted in North America (n = 7) and the European Union (n = 5). More than half of the studies were published after 2020 (n = 10). Our analyses highlight key aspects of selected studies, including bibliometric metadata, study attributes (e.g., study types, methods, and data sources), and thematic findings. Statistical modeling (n = 8) and machine learning (n = 4) are the most widely used study methods. Majority (n = 11) of the publications are single-site studies, while the other multi-site collaborations (n = 6) have emerged among hospitals, academic institutions, and research institutions.

Discussion: Sex-specific disparities in cognitive decline and impairment remain a critical issue in healthcare. Most informatics research has primarily concentrated on identifying generic sex differences in cognitive decline and impairment progression, rather than exploring the complex underlying mechanisms such as observational studies with causal analysis. While these studies are valuable, they lack a holistic approach to understanding sex-specific disparities.

Conclusion: There is a significant gap in using informatics to understand how biological, social, and behavioral factors contribute to sex-specific disparities in cognitive decline and impairment. This limitation underscores the need for more comprehensive informatics research that goes beyond mere identification to find the root cause of these disparities in healthcare.

Background: Memory impairments are highly prevalent in patients with epilepsy, yet important gaps remain in the understanding of potential sex and gender differences. This systematic review and meta-analysis aim to synthesize the available evidence on sex and gender differences in memory functioning in adults and children with epilepsy, and to explore the relevance of the epilepsy type, the side of seizure focus, the hemispheric dominance for language, the educational level and the age group in these differences.

Methods: The study followed PRISMA guidelines and was registered in PROSPERO (CRD420251006928). Studies were retrieved from Web of Science, PubMed/MEDLINE, Embase, and Scopus.

Results: The systematic search yielded 1,261 records, from which 32 studies were selected. Women scored higher than men in immediate verbal memory, both at baseline (g = 0.34; 95% CI = 0.23, 0.44; p < 0.0001) and after epilepsy surgery (g = 0.30; 95% CI = 0.15, 0.44; p < 0.0001). This advantage was also observed in delayed verbal memory, at baseline (g = 0.30; 95% CI = 0.19, 0.41; p < 0.0001) and after surgery (g = 0.25; 95% CI = 0.09, 0.41; p = 0.0018). In contrast, men outperformed women in immediate visual memory, both before (g = -0.13; 95% CI = -0.22, -0.03; p = 0.01) and after surgery (g = -0.17; 95% CI = -0.33, -0.01; p = 0.04). No significant differences were observed in working memory or delayed visual memory. Effect sizes favoring women in verbal memory were significantly smaller in studies including only patients with temporal lobe epilepsy compared to mixed epilepsy types. The effect size for postsurgical delayed verbal memory was moderated by the side of seizure focus: studies including a greater proportion of patients with left-hemisphere epilepsy showed poorer postsurgical delayed verbal memory. Hemispheric dominance for language, age, and educational level did not moderate sex-gender differences in memory.

Conclusions: These findings underscore the importance of incorporating sex and gender variables in neuropsychological assessment and intervention planning, offering evidence-based recommendations.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease. An increasing body of evidence indicates that hormones, particularly estrogen, play a significant role in RA. To date, no bibliometric studies have been conducted specifically on the role of estrogen in RA. This study seeks to perform a bibliometric analysis to elucidate research trends concerning estrogen in the context of RA from a comprehensive and systematic viewpoint.

Methods: We extracted literature pertaining to estrogen in RA from the Web of Science Core Collection (WOSCC) database, up to April 22, 2025. Research trends in this domain were analyzed utilizing bibliometric software tools, VOSviewer and Bibliometricx.

Results: A total of 1,009 literatures were included in this study. Articles in this field were first published in 1951 and have shown an overall upward trend since 1982. The United States and China were the countries that contributed the most articles, while the University of Genoa was the most contributing affiliation. CUTOLO M is the most prolific and most cited author. Arthritis and Rheumatology is the most published and cited journal in this field in the world. The primary focus of research in this area encompasses the evidence, mechanisms, and practical applications of estrogen's involvement in RA. In addition, the key words such as "cytokines", "inflammation", "immune response", "oxidative stress", and "endometriosis" appear most frequently, which indicates that the mechanism research of estrogen's participation in RA has been a research hotspot in recent years.

Conclusion: This study reflects the degree of academic interest in the potential link between estrogen and RA. This also lays a foundation for continuous research in this field and provides certain insights for future research directions.

Background: Bone morphogenetic proteins (BMPs) have been reported in many studies to be related to adult neurogenesis. Neurogenic impairment is a hallmark of Alzheimer's disease (AD), while the involvement of BMPs remains unclear.

Methods: AD models were established using APP^NL-G-F transgenic mice and C57BL/6 mice subjected to intracerebral injection of Aβ_(25-35) peptide. Female APP^NL-G-F mice received pharmacological inhibitor treatment, whereas Neuro2a cells were exposed to estrogen stimulation in vitro. Immunofluorescence staining was conducted to evaluate hippocampal neural stem cell proliferation. The hippocampus and cellular pellets were isolated, and quantitative PCR (qPCR) was employed to determine mRNA expression levels.

Results: Our study revealed that APP^NL-G-F mice and Aβ-injected mice exhibited impaired neurogenesis in the brain, with a clear sex-dependent difference only in APP mice. Several BMPs were markedly upregulated in the hippocampus of AD model mice, with significantly higher expression in females than in males. BMP inhibitor attenuated neural stem cell proliferation deficits in female APP^NL-G-F mice. Estrogen stimulation robustly enhanced BMP6 expression in Neuro2a cells.

Conclusions: Our findings reveal a sex-dependent impairment of neurogenesis in APP^NL-G-F mice driven by BMP signaling. Blocking BMP signaling enhances adult neural stem cell proliferation in female APP^NL-G-F mice, providing a potential therapeutic target for AD.

Background: The ventral premammillary nucleus (PMv), situated within the ventrobasal hypothalamus, is sensitive to steroid hormones and is involved in pheromone-responsive circuits. It maintains robust connections with sexually dimorphic nuclei both within and beyond the hypothalamus. Investigations over the past 15 years have suggested the role of the PMv in integrating environmental cues from conspecifics with internal states, thereby facilitating appropriate physiological and behavioral responses during reproductive and agonistic interactions. Neurochemical evidence indicates sexual dimorphism in the PMv of rats; however, comprehensive structural analyses are lacking.

Methods: After perfusing and processing the brains of male and female rats during the estrus and diestrus phases, we applied stereological methodology in the PMv.

Results: Males presented significantly greater neuronal volume and quantity than females did across both cycling phases. Neuronal volume in females was notably greater during estrus than during diestrus. However, no dimorphism was detected in overall volume, neuronal density, volume occupied by neurons, or neuropils.

Conclusions: Given its role as a nexus between nutritional status and reproductive physiology, as well as its involvement in modulating agonistic behavior, including maternal aggression, structural disparities in the PMv between males and females may reflect divergent functional roles, contributing to sex-specific strategies in reproduction and aggression.

Objective: Volumes of the hippocampus and amygdala, both major hubs for neural stress regulation amongst others, are associated with social stressors, cortisol awakening response (CAR) and sex. Importantly, the interplay of these different factors in affecting the morphology of both brain regions remains unclear. This study aimed to elucidate the intricate influence of these factors on grey matter volumes (GMV) of the hippocampus and amygdala.

Methods: We analyzed associations between structural brain data, self-reported chronic social stress (including subscales on social tension, social overload, lack of social recognition and social isolation) and CAR of 83 healthy participants (40 females) with multiple regression analyses.

Results: In males, but not females, higher levels of social tension were associated with lower bilateral hippocampal GMV. Amygdala GMV was related to CAR and social stress, with social overload being associated with reduced amygdala GMV in individuals not showing the typical CAR (reflecting a blunted physiological response to awakening), while the opposite pattern emerged in those with a typical CAR.

Conclusions: The association between chronic social stress and HC and AMY volume is interacting with CAR-pattern and sex. The brain morphology in males and in individuals with an atypical CAR showed reductions in association with chronic social stress. Our findings point to a complex interaction between social stress, cortisol patterns, sex and brain architecture, which needs to be assessed in more detail in future research.

Background: Cardiovascular risk factors are determinants of coronary artery calcium (CAC) progression. However, whether the effect of cardiovascular risk factors on CAC progression among participants with CAC = 0 differs by sex remains unclear.

Method: This study included 1815 participants 33-45 years of age from the Coronary Artery Risk Development in Young Adults study at baseline who had CAC measured both at baseline and five years later. CAC was measured using computed tomography. Risk factor measurements included body mass index (BMI), waist circumference, total cholesterol, triglycerides, glucose, systolic blood pressure (BP), low-density lipoprotein cholesterol, and smoking status.

Results: CAC progression was significantly higher among men than women (2.25 (8.68) vs. 0.89 (6.7), P < 0.0001). In the restricted cubic spline models, the associations between systolic BP and CAC progression in women followed a nonlinear relationship. The slope for the regression of systolic BP on CAC progression in women was relatively flat until around 125 mmHg of systolic BP and then started to increase rapidly afterwards, with a β of 0.16. BMI was associated with CAC progression only in men. Similar associations were observed when replacing BMI with waist circumference. There were no sex differences in the associations between CAC progression and smoking.

Conclusion: Systolic BP in women and BMI (and/or waist circumference) in men may have different contributions to CAC progression between the sexes among participants with CAC = 0. Our study provides evidence that understanding sex differences in cardiovascular risk factors is essential for implementing targeted interventions to prevent CAC progression.

Background: Despite growing recognition of sex differences in medicine, little is known about their role in neonatology, particularly among extremely premature infants (EPI, < 28 weeks gestation), who face high morbidity and mortality driven by infections. Antibiotics therapy is widely used but may alter cellular metabolism, leading to adverse drug reactions. However, pharmacological studies in EPI remain limited, and sex-dependent effects of antibiotic treatments are largely unexplored. This study investigated sex-related metabolomic differences in EPI in relation to antibiotic exposure.

Methods: Targeted mass spectrometry (MS) was applied to dried blood spots (DBS) collected within the neonatal screening program of the Campania region (Italy) between 2018 and 2023. Amino acids (AA) and acylcarnitines (AC) were quantified in 116 EPI stratified by sex and antibiotics treatment.

Results: Untreated EPI of both sexes showed largely comparable metabolic profiles, with the exception of higher C16OH levels in males. Antibiotic treatment, however, markedly amplified sex-dependent divergence, with male EPI displaying significantly elevated AC concentrations (C0, C2, C3, C4, C5, C6, C5OH, C10:1, C16:1, C18, C18:1) compared to females. Stratification by penicillins + aminoglycosides treatment revealed distinct patterns: in EPI treated with a penicillins + aminoglycosides combination, males exhibited higher levels of C0, C2, C4, C6, C16:1, C18, and C18:1, while C3, C5, C5OH, and C10:1 no longer differed by sex. Furthermore, eight additional AC (C3DC, C14:1, C14, C16, C10DC, C16OH, C4OH, C16:1OH) were significantly elevated in treated males, differences that were not detected when all antibiotic classes were pooled.

Conclusions: These findings demonstrate that standard empirical antibiotic therapies for prematurity exert sex-dependent effects on neonatal metabolism, with antibiotics amplifying AC alterations in males. Our results underscore the need to consider sex as a key biological variable in neonatal pharmaco-metabolomics and highlight the potential of metabolic profiling to optimize individualized treatments in EPI.

Background: Up to 80% of Alzheimer's disease (AD) patients suffer from brain vascular damage resulting in multi-etiology dementia (MED). Sex is a well-known risk factor for dementia; out of three AD patients two are women. 17β-estradiol, a predominant ovarian hormone in woman before menopause, is known to have beneficial effects on the cerebrovasculature, neuroinflammation and neuroprotection. Here, we investigated the consequences of the loss of ovarian hormones caused by surgical menopause (ovariectomy) on AD and MED.

Methods: The App^NL-F knock-in mice were used to model AD. At about 5.5 months of age, a stage corresponding to early disease pathology, female App^NL-F mice were subjected to ovariectomy (OVX) or sham surgery (Intact) and left to recover for 3 weeks to clear any endogenous gonadal hormones. In half of the mice from each group, MED was modeled using chronic cerebral hypoperfusion (unilateral carotid artery occlusion), a model of vascular contributions to cognitive impairment and dementia (VCID). Control animals (AD only model) received sham surgery. Mice were then subjected to a battery of behavioral tests before being euthanized and brains were collected to assess pathology.

Results: We found that loss of ovarian hormones impairs spatial learning and memory, impairs activities of daily living, and affects underlying pathology including compromising microglial response. Some of these effects were exacerbated by cerebral hypoperfusion (VCID).

Conclusions: These results shed light on the effects of ovarian hormone loss after surgical menopause in female mouse model of AD and MED in order to better understand sex-specific risk factors.

Sexual dimorphism has been implied to certain human physiology and diseases. This topic has recently garnered more attention, highlighting individual variances in precision medicine and individualized clinical trials. It is recognized that individual gene expression variations in males and females could have profound physiological impacts. Tissue specific expression profiles determine protein-coding gene activities and contribute additional physiological variations. Therefore, tissue specific gene expression profiles should be comprehensively analyzed among individual human subjects. In this report, we developed a user-friendly bioinformatic tool to visualize gene expression levels and variances across tissue samples, aiming to facilitate research into potential sexual dimorphism genes. The Gini coefficient metric was used with the most recent GTEx V10 datasets to examine variations in the expression profiles of human protein-coding genes across 43 tissue subtypes. Next, these variations were specifically evaluated using the Gini coefficient index for male and female individuals across all tissue subtypes. Our web-based visualization tool generated tissue specific expression profiles for individual male and female samples. It concurrently illustrates expression levels and variation comparisons between male and female groups across all tissue subtypes. Although most protein-coding genes had similar expression variation patterns between the two sexes, several genes exhibited distinct variations for some tissue subtypes, as indicated by their significant Z-scores in Gini index disparities. Users can explore differentially expressed protein-coding genes across tissue subtypes or search for genes of interest in the Tissue Prominent Sexual Dimorphism Gene database ( https://tpsdg.ibms.sinica.edu.tw ). This database can be employed to visualize expression levels and variations among individual samples within specific tissues, thereby facilitating future research into divergently expressed protein-coding genes in the human population.