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At least 19 recordsLinked to original sources

PubMed2025

The skeletal muscle of aged male mice exhibits sustained growth regulatory transcriptional profile following glucocorticoid exposure compared with young males.

Excess glucocorticoids induce skeletal muscle myopathy by changing gene expression. Advanced age augments glucocorticoid-mediated muscle phenotypes, yet the transcriptional responses underlying those augmented phenotypes are unclear. The purpose of this study was to define the glucocorticoid-responsive transcriptome in young and aged muscle following both acute and more prolonged glucocorticoid treatment. Young (4-mo-old) or aged (24-mo-old) male mice were administered either an acute injection of dexamethasone (DEX) or vehicle or daily DEX or vehicle injections for 7 days. Muscles were harvested 6.5 h after the final or only injection. The tibialis anterior (TA) was selected for RNA sequencing analysis as DEX treatment lowered TA mass specifically in aged males. In silico analyses identified enriched pathways and transcription factors predicted to regulate DEX-sensitive genes. Acute DEX altered similar numbers of genes in young (950) versus aged males (913), although aged males had greater magnitudes of fold change. After 7 days of DEX treatment, aged muscle exhibited more DEGs compared with acute exposure (1,196 vs. 913), whereas young muscle exhibited fewer DEGs than after acute exposure (599 vs. 950). In aged males, glucocorticoid-sensitive genes were consistently enriched for growth regulatory processes across both time points, a pattern that was not evident in young males. Despite those age-associated transcriptional differences, the transcription factors predicted to regulate the glucocorticoid-sensitive genes were similar in young and aged males. These data expand our understanding into how aging modifies the transcriptional response to excess glucocorticoids in skeletal muscle.NEW & NOTEWORTHY Glucocorticoids promote mass loss in certain muscles with advanced age but not at younger ages. In a muscle whose mass is lost in response to elevated glucocorticoids only in advanced age in males, we show that glucocorticoids initiate a unique and exaggerated transcriptional profile after both acute exposure to the hormone and after prolonged treatment that is consistent with muscle atrophy. These findings expand our understanding of the effect primary aging has on glucocorticoid-induced atrophy in males.

Animals↗

PubMed2026

Epigenetic maintenance of male reproductive longevity: SIRT7 as a guardian of male germline genome integrity†.

Explore the source record for details and available documents.

Journal Article↗

PubMed2025

Interaction of host gene-gut microbiota in male grading of Macrobrachium rosenbergii.

UNLABELLED: The giant freshwater prawn (GFP; Macrobrachium rosenbergii), a crustacean of high nutritional and economic value, is crucial for aquaculture. During the same growth cycle, male GFPs develop into three distinct forms: small males, orange claw males, and blue claw males. These morphotypes display varying social behaviors, which severely constrain their industrial development. To address this, this study collected male GFP samples at critical developmental time points (100, 110, and 120 days post-hatching) for phenotypic trait measurement and analysis to obtain external morphological data. Through gut microbiota diversity analysis, we identified key gut bacteria (Lactococcus garvieae and Lactobacillus taiwanensis) influencing male morphotype differentiation. Transcriptomic analysis revealed host Kyoto Encyclopedia of Gene and Genome pathways and key genes (Wnt-6, CTSB, CTSL, PPAE, and TP53) associated with morphotype differentiation. The interactions among phenotypic traits, gut microbiota, and key genes were systematically studied through association analysis. Weighted gene co-expression network analysis was employed to construct co-expression modules, from which critical gene modules influencing phenotypic variation were identified. Through association network analysis, we established an "Achromobacter-CD-TRINITY_DN93139_c0_g2 (calpain clp-1)" interaction model. Our findings provide novel insights into the genetic enhancement of GFPs and offer guidelines for future research regarding gut symbiotic bacteria and breeding initiatives. IMPORTANCE: Male Macrobrachium rosenbergii (giant freshwater prawn [GFP]) in the same growth cycle will develop into small males, orange claw males, and blue claw males. This individual heterogeneity in growth significantly impacts the benefits of aquaculture. However, the factors influencing the differentiation of male GFP morphotype remain unclear. This study analyzed the phenotypic data of various GFP levels, the structure of the intestinal microbiota, and the differential genes within the gonadal transcriptome at critical time points of male GFP-level type differentiation. The aim was to explore the potential role of intestinal microbiota and differential genes in this phenomenon. This study offers new insights into the research on the phenomenon of male GFP-level type differentiation.

Animals↗

PubMed2017

Single-sperm sequencing reveals the accelerated mitochondrial mutation rate in male Daphnia pulex (Crustacea, Cladocera).

Mutation rate in the nuclear genome differs between sexes, with males contributing more mutations than females to their offspring. The male-biased mutation rates in the nuclear genome is most likely to be driven by a higher number of cell divisions in spermatogenesis than in oogenesis, generating more opportunities for DNA replication errors. However, it remains unknown whether male-biased mutation rates are present in mitochondrial DNA (mtDNA). Although mtDNA is maternally inherited and male mtDNA mutation typically does not contribute to genetic variation in offspring, male mtDNA mutations are critical for male reproductive health. In this study, we measured male mtDNA mutation rate using publicly available whole-genome sequences of single sperm of the freshwater microcrustacean Daphnia pulex Using a stringent mutation detection pipeline, we found that the male mtDNA mutation rate is 3.32 × 10-6 per site per generation. All the detected mutations are heteroplasmic base substitutions, with 57% of mutations converting G/C to A/T nucleotides. Consistent with the male-biased mutation in the nuclear genome, the male mtDNA mutation rate in D. pulex is approximately 20 times higher than the female rate per generation. We propose that the elevated mutation rate per generation in male mtDNA is consistent with an increased number of cell divisions during male gametogenesis.

Animals↗

PubMed2026

Maternal obesity in rats results in male-specific increases in genome-wide DNA methylation in postnatal offspring liver.

Male-specific peripubertal DNA demethylation in the liver has been reported in mice. Here, we investigated whether it also occurs in rats, the influence of maternal obesity and whether DNA demethylation changes contribute to observed sex-specific effects of maternal obesity in offspring. Female rats were fed a high-fat, high-sugar 'cafeteria' (Caf) diet before mating with standard chow-fed males. The offspring liver methylome and transcriptome were examined. Body weight was higher in Caf-fed dams prior to mating, during gestation and at parturition. Male and female offspring from Caf-fed dams had lower birth weights but higher adult weights and adiposity than offspring from chow-fed dams. A comparison of DNA methylation in 3-week-old weaner males versus female siblings from chow-fed dams did not reveal the male-specific DNA demethylation that was previously reported in mice. However, strong maternal diet effects in male weaner offspring methylation were observed. A comparison of female weaners from chow- versus Caf-fed dams showed a range of differences, with 39% of differentially methylated regions (DMRs) having higher methylation in Caf offspring and 61% of DMRs having higher methylation in chow offspring. In stark contrast, 99% of maternal-diet-induced DMRs in male weaner offspring had higher methylation in offspring from Caf-fed dams. This suggests that maternal obesity induces widespread hypermethylation in the male offspring liver at weaning. However, a comparison with RNA sequencing data revealed limited transcriptional changes at this developmental stage or in adult offspring. While these data highlight how environmentally sensitive DNA methylation is in the male rodent perinatal period, these methylation changes may not be a major contributor to sex differences in developmentally programmed liver disease.

Animals↗

PubMed2025

Mendelian randomization reveals causal relationships between cytokines and male reproductive diseases.

This study aims to explore the causal links between cytokines and four male reproductive disorders, namely abnormal spermatozoa (AS), male infertility, erectile dysfunction (ED), and hyperplasia of prostate (HP), employing a two-sample Mendelian randomization (MR) approach. Genetic associations with male reproductive diseases were derived from the IEU OpenGWAS project, with cytokine data from two GWASs focused on the human proteome and cytokines. Estimations were derived using inverse variance weighting, MR-Egger regression, weighted median, weighted model, and simple mode. Furthermore, the robustness of the findings was evaluated through Cochran's Q-test, MR-Egger regression, and leave-one-out sensitivity analysis. Fifteen unique cytokines were identified as having causal relationships with the risk of four male reproductive disorders. Specifically, for AS, interleukin-22 (IL-22), IL-12, and macrophage migration inhibitory factor were negatively correlated with AS, while tumor necrosis factor β levels were positively correlated with AS. In the context of male infertility, IL-2 receptor antagonist levels, IL-34, and granulocyte-colony stimulating factor levels were positively linked to male infertility, whereas IL-21 showed a negative relationship. Regarding ED, IL-19, IL-1β, and eotaxin levels were negatively associated with ED risk, while macrophage inflammatory protein 1β (MIP-1β) levels and interferon gamma-induced protein 10 levels were positively associated. As for HP, stromal-cell-derived factor 1α levels and MIP-1α levels revealed negative associations with HP. In conclusion, this MR analysis revealed that several cytokines were causally associated with male reproductive diseases and could be valuable in offering new insights for further mechanistic and clinical investigations of cytokines-associated male reproductive diseases.

Male↗

PubMed2026

Male and Female Mice Show Similar Fear Memory Performance Despite Hippocampal Immediate Early Gene Expression Differences During Encoding and Consolidation.

Accurate and efficient memory processing is essential for survival. A body of ongoing work in both human subjects and animal models suggests that memory processing may differ substantially between males and females. In mice, contextual fear memory (CFM) encoding, consolidation, and recall have been well studied, and the mouse hippocampus and amygdala have been implicated in these processes. The present pilot study addresses whether the activation of these brain regions differs substantially between male and female mice at each stage of CFM processing. We find that male and female mice show no differences in sleep behavior, which is essential for CFM consolidation, following single-trial contextual fear conditioning (CFC). We also find no significant differences in CFM recall performance between male and female mice. However, females show a trend for larger increases in CA1 cFos expression, relative to males, during CFM encoding. On the other hand, only males-but not females-show an apparent increase in cFos expression among dentate gyrus (DG) granule cells during CFM consolidation. Males also show a trend for a larger apparent reduction in cFos in CA1 and CA3 during CFM consolidation, relative to females. These preliminary findings highlight the idea that the neurobiological underpinnings of memory processing may differ between males and females, even when performance during recall is identical.

Animals↗

PubMed2025

Alternative splice acceptor site in MSH4 gene is responsible for male sterility conferred by ms5 in soybean.

In soybean breeding, using the recessive male-sterile ms5 gene, derived from fast neutron mutagenesis, for recurrent selection is advantageous because of the d2 locus, which controls cotyledon color in mature seeds and can be used as a phenotypic selection marker for ms5 male sterility. However, occasional self-fertilization occurs because of the elimination of d2 linkage and instability of male sterility. Elucidating the mechanism and the gene responsible for ms5 male sterility may resolve these problems. Using fine mapping with 15 simple sequence repeat (SSR) markers, we narrowed down the candidate ms5 locus to a 54-kbp region. Bulked-DNA analysis using next-generation sequencing revealed a deletion as a candidate variation in the region. This 15-bp deletion and a nucleotide substitution were identified in intron 1 of MutS homolog (GmMSH4), which modulates chromosomal recombination in meiosis. The ms5 transcript contained a novel exon with a premature termination codon. This exon originated from an alternative splice acceptor site caused by the deletion and nucleotide substitution, disrupting gene function. Co-segregation of male sterility with five independent mutations in GmMSH4 was confirmed using progeny of mutant lines. Mutations in GmMSH4 led to biased DNA partitioning during meiosis, resulting in collapsed or enlarged pollen and suggesting that ms5 male sterility is caused by the failure of pollen formation during meiosis due to the loss of function of GmMSH4. These findings could help explain the mechanism of instability of ms5 male sterility and improve the efficiency of recurrent selection using DNA markers in soybean breeding.

Glycine max↗

PubMed2026

Association between seminal and serum iron parameters and male infertility: a systematic review and meta-analysis.

BACKGROUND: Iron is an essential trace element for normal spermatogenesis, yet excessive iron accumulation may impair male fertility. Preliminary studies imply a link between elevated iron levels and male infertility, but evidence remains limited without systematic quantitative synthesis. This metaanalysis assessed the association between iron concentrations and male infertility. METHODS: We systematically searched PubMed, CBM, CNKI and Cochrane Library. RevMan, Stata and R were used for data analysis. Randomeffects models pooled effect sizes, with forest and funnel plots generated to evaluate seminal and serum iron levels in male infertility. RESULTS: After screening studies published up to April 2025, a total of ten eligible articles involving 985 participants were finally included in this meta-analysis. Pooled results revealed that seminal and serum iron concentrations were notably higher in infertile males compared with fertile controls. Specifically, infertile men presented higher seminal iron levels (SMD = 0.44, 95% CI: 0.12-0.76, P < 0.05), as well as elevated serum iron levels (SMD = 3.77, 95% CI: 1.68-5.87, P < 0.05). The present results suggest that increased seminal and serum iron concentrations may be potentially correlated with male infertility risk.

Humans↗

PubMed2026

Exploring Primary Care Clinicians' Sexual and Reproductive Health Care Delivery to Male Adolescents and Young Adults.

INTRODUCTION: Despite existing guidance for adolescent sexual and reproductive health (SRH) care, male adolescent SRH care receipt is inadequate. Limited research has explored factors affecting clinicians' provision of SRH care to male adolescents, specifically. METHODS: This mixed-method study with 12 primary care clinicians included a brief survey assessing care delivery practices and confidence, followed by an in-depth interview to explore factors affecting SRH care delivery. RESULTS: Clinicians reported high confidence delivering male adolescent SRH care (mean ± SD: 8.31 ± 1.71 out of 10), but delivered only about half the recommended services (20 items out of 38). Factors influencing care delivery included gaps in education/training, assumptions about male SRH care, and behavioral constraints at various levels. DISCUSSION: Findings underscore the need to strengthen male adolescent SRH care by enhancing provider training, increasing clinic-level supports, and addressing structural barriers. CONCLUSIONS: Findings can inform strategies to improve the quality and comprehensiveness of SRH services for male adolescents in primary care settings.

Humans↗

PubMed2026

Opposite metabolic and gut responses to oral glutamine in male and female mice with diet-induced obesity.

Obesity is often associated with sex-dependent metabolic complications, to which altered intestinal barrier function and gut microbiota contribute. Glutamine supplementation has previously shown beneficial effects on gut barrier function and glycemic control. We thus aimed to characterize, in male and female mice, the effects of oral glutamine supplementation during high-fat-diet-induced obesity. Male and female C57BL/6 mice received a standard (SD) or high-fat diet (HFD; 60 % kcal from fat) for 14 weeks (W14). From W12 onward, mice received glutamine in drinking water (2 g/kg/day) or no supplementation. Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic inflammatory response, cecal microbiota and inflammatory/endocrine adipose response were assessed. In both male and female mice, glutamine supplementation failed to improve body weight and body composition. However, glutamine reduced glucose intolerance in HFD-fed males (AUC reduced by 14.57 %) that was associated with a partial restoration of plasma resistin and insulin and a trend toward limiting adipose inflammatory response. In males, glutamine did not affect gut microbiota composition and colonic response. Conversely, in HFD-fed females, glutamine supplementation led to gut microbiota changes (increase in Bacteroidota and Pseudomonadota phyla; increase in Muribaculaceae and Tannerellaceae families), increased colonic inflammatory markers (Il1b, Tlr4, Myd88, Irf3), increased inflammatory response in subcutaneous adipose tissue and increased HOMA-IR. Finally, HFD-fed mice exhibited sex-specific responses to glutamine supplementation with protective effects in males and harmful effects in females that need to be further deeply explored.

Animals↗

PubMed2026

Sex-specific expression of detoxification proteins contributes to differential metabolic detoxification capacity and acaricide sensitivity in female and male Tetranychus cinnabarinus (Boisduval).

Pronounced sex-specific differences exist in the toxicological traits of spider mite species. Our previous work showed that female Tetranychus cinnabarinus exhibit significantly higher tolerance to acaricides than males, primarily driven by elevated detoxification enzyme activity. However, the molecular basis underlying this sex-specific difference remains unclear. Here, we used pyridaben and cyflumetofen as representative acaricides to dissect the molecular mechanisms underlying sex-specific differences in detoxification metabolism between female and male mites. After 48 h of cyflumetofen exposure, GST activity increased significantly in female mites. Following pyridaben exposure, the activities of both P450 (24 h and 48 h) and CCE (48 h) increased significantly in female mites. Under the same conditions, only P450 activity increased significantly in male mites after 48 h of pyridaben exposure. Proteomic profiling identified 33 differentially expressed detoxification enzymes, predominantly from the major detoxification families P450, GST, and CCE; among them, 26 were significantly upregulated in females relative to males. Six detoxification enzymes, including CYP392A3, CYP389C5, TcGSTd02, TcGSTd13, TcCCE39, and TcCCE52, were selected for functional characterization. We successfully obtained six active recombinant detoxification enzymes through heterologous expression. IC50 and in vitro metabolism assays showed that these recombinant proteins display both shared and distinct capacities for metabolizing or sequestering cyflumetofen and pyridaben. RNAi and bioassay results demonstrated that silencing CYP389C5, TcGSTd02, and TcCCE52 resulted in more pronounced changes in acaricide susceptibility in female than in male mites. Collectively, this study demonstrates that the sex-biased protein abundance identifies candidate biochemical contributors to differential susceptibility in female and male mites.

Animals↗

PubMed2026

Plasmacytoid dendritic cell-mediated L-glutamate catabolism links gut microbiota to male infertility.

Emerging evidence suggests that gut microbiota composition influences male reproductive health; however, the immunometabolic mechanisms underlying this association remain insufficiently characterized. We investigated whether specific immune cell-mediated metabolic pathways, particularly plasmacytoid dendritic cell (pDC)-driven L-glutamate catabolism via the hydroxyglutarate pathway, contribute to the causal link between gut microbiota and male infertility. We conducted a 2-sample, 2-step Mendelian randomization (MR) analysis using inverse-variance weighting as the primary estimator and Bayesian weighted MR for robustness. Exposure data comprised 412 gut microbial taxa/metabolic pathways and 731 immune cell phenotypes from large European-ancestry genome-wide association studies. Male infertility genome-wide association studies data (1429 cases; 128,710 controls) were obtained from FinnGen R10. Only exposure-mediator-outcome pairs meeting stringent pleiotropy, heterogeneity, and reverse-causality criteria were retained for mediation analysis. Nine microbial taxa/metabolic pathways and 18 immune traits exhibited putative causal associations with male infertility. The L-glutamate degradation V pathway via hydroxyglutarate was linked to reduced infertility risk (inverse-variance weighting odds ratio [OR] = 0.68; 95% confidence interval, 0.52-0.89; P = .005). Two-step MR suggested that forward scatter area on pDCs may mediate this association, although the mediation effect was imprecise (effect = 0.0277; 95% confidence interval, -0.0348 to 0.0903). This study provides suggestive genetic evidence that pDC-mediated glutamate catabolism may connect gut microbial metabolic activity to male infertility. These findings highlight immunometabolic pathways as testable targets for mechanistic validation and microbiota-directed interventions.

Male↗

PubMed2026

A duplicated female pathway gene figla-like evolves as the male sex-determining gene in tilapia.

As the largest group of vertebrates, fish exhibit frequent turnover of sex-determining (SD) genes. Here, we assemble a chromosome-level YY red tilapia genome and identify figla-like (figlal) as the SD gene on tilapia linkage group (LG) 1. Integrative phylogenetic and genomic evidence suggests that figlal originated from a tilapia-specific duplication and transposition of the ancestral bHLH family gene figla from LG12 to LG1. Fluorescence in situ hybridization reveals expression divergence between figla and figlal, with figla expressed in female oocytes and figlal expressed in male gonadal somatic cells during early gonadal differentiation. The shift in expression after duplication might be driven by the insertion of cis-regulatory elements mediated by transposable elements. Knockout of figlal in XY fish results in male-to-female sex reversal as indicated by ovarian morphology, down-regulation of the male pathway gene dmrt1, and up-regulation of the female pathway gene cyp19a1a in the gonads. In contrast, overexpression of figlal in XX fish induces female-to-male sex reversal. These findings implicate figlal as an SD gene on tilapia LG1 and reveal the history of a unique evolutionary innovation in which a female oocyte gene evolved into a male SD gene via duplication, transposition, and cis-regulatory rewiring.

Animals↗

PubMed2025

Tdrd15 is dispensable for male fertility and spermatogenesis in the golden hamster.

Tudor domain-containing proteins (TDRDs) constitute an evolutionarily conserved protein family and are critical for germline development and piRNA pathway regulation, with established roles in male fertility. While multiple TDRD family members have been functionally linked to spermatogenic impairment, the precise biological role of TDRD15 remains to be elucidated. We used CRISPR/Cas9-mediated gene editing to generate Tdrd15 knockout (KO) golden hamsters (Mesocricetus auratus), a model necessitated by the absence of a functional Tdrd15 ortholog in the mouse genome, to investigate its function in male reproduction. Phylogenetic analysis demonstrated that TDRD15 is strongly conserved among eutherian mammals, with testis-restricted expression patterns in hamsters. Despite the successful induction of frameshift mutations and significant transcriptional knockdown, Tdrd15 KO males maintained normal fertility parameters, including unaltered testicular architecture, spermatogenic progression (confirmed by periodic acidic-Schiff (PAS) staining and immunohistochemistry), and sperm quality metrics determined using a computer-assisted analysis. Quantitative polymerase chain reaction (qPCR) revealed compensatory overexpression of paralogous Tdrd genes in KO testes, implying functional redundancy within this protein family. This study provides the first experimental evidence that TDRD15 is dispensable for male fertility in golden hamsters under physiological conditions, thereby challenging the prevailing assumptions of its obligatory function in spermiogenesis. Altogether, these findings support a more targeted allocation of research efforts within the field of male reproductive biology.

Animals↗

PubMed2026

Male accessory gland proteins in Grapholita molesta: Identification and reproductive functional validation of four accessory gland-specific lipases.

Accessory gland proteins (Acps), synthesized in the male accessory glands (AGs), are transferred to females via spermatophores during mating and elicit diverse post-mating physiological and behavioral responses. However, Acps have not been comprehensively characterized in Grapholita molesta, a cosmopolitan orchard pest. Here, using data-independent acquisition mass spectrometry, we describe an integrated proteomic approach combining comparative AG analyses (virgin vs. newly mated) with spermatophore profiling to identify Acps in G. molesta. According to the established screening criteria, we identified 83 confirmed Acps, which were classified into nine categories. Tissue-specific expression patterns of 20 randomly selected Acp genes were evaluated, revealing that these genes were specifically or highly expressed in male AGs. Among the 83 confirmed Acps, four Acps harbored the PLN02872 superfamily domain and were classified into the canonical lipase family. Notably, their transcripts were all highly expressed in the AGs during the pre-maturation stage. These four Acps were selected for preliminary validation of their male reproductive functions. RNAi-mediated knockdown of three out of four lipase genes in G. molesta males significantly decreased the fertility of mated females, with phenotypes including a significant reduction in egg production and egg hatching rate. This study provides a comprehensive catalog of high-confidence Acps, lays a foundation for subsequent in-depth functional characterization of these reproductive proteins, and offers promising molecular targets for the development of novel genetic regulation-based integrated pest management strategies.

Animals↗

PubMed2026

Effect of urinary catheter securement band on meatal pressure injury in male intensive care patients: A randomized controlled trial.

OBJECTIVES: To investigate the effectiveness of a urinary catheter securement band in preventing meatal pressure injury (meatal-PI) in male ICU patients, and to identify associated risk factors and the timing of injury development. METHODS: A total of 248 adult male ICU patients were randomly allocated to an intervention group (n = 124) or a control group (n = 124) between December 2024 and April 2025. The intervention group received a catheter securement band in addition to standard care, while the control group received standard care alone. Meatal-PI was evaluated daily using a structured monitoring form and a validated staging system. RESULTS: The incidence of meatal-PI was significantly lower in the intervention group (6.5%) compared with the control group (16.1%) (p = 0.016). Multivariate analysis identified catheter securement, use of silicone catheters, higher Braden Scale scores, and shorter ICU length of stay as independent protective factors, while advanced age was associated with increased risk. Additional factors significantly associated with meatal-PI included comorbidities, higher device burden, latex catheter use, dry skin, lower Glasgow Coma Scale and Braden scores, sedation, and perineal oedema (p < 0.001). CONCLUSIONS: The use of a catheter securement band significantly reduces the incidence of meatal-PI in male ICU patients. Incorporating catheter securement devices into routine nursing care, prioritising silicone catheter use, and performing regular meatal assessments may enhance patient safety by reducing the risk of device-related pressure injuries. Further research comparing different catheter securement methods across diverse patient populations is warranted. IMPLICATIONS FOR CLINICAL PRACTICE: The use of catheter securement bands may reduce the incidence of meatal-PI in male ICU patients. Incorporating standardized catheter stabilization strategies into routine intensive care nursing practice may enhance patient safety and support pressure injury prevention efforts.

Humans↗

PubMed2026

Molecular and immune profiling of HER2-low, HER2 ultra-low, and HER2-null male breast cancer.

BACKGROUND: HER2 expression is described along a biological continuum from null to positive and serves as a critical biomarker for therapeutic guidance in breast cancer (BC). While HER2-low and ultra-low categories have emerged as actionable targets for antibody-drug conjugates (ADCs) in female BC, their molecular and immune characteristics remain largely unexplored in male breast cancer. METHODS: We profiled 214 male breast tumors using next-generation sequencing and whole-transcriptome sequencing to assess mutational, transcriptomic, and immune landscapes. Tumor mutational burden (TMB) was defined as high if > 10 mutations/Mb. Immune cell fractions were inferred using Quantiseq deconvolution. RESULTS: Among 214 samples, 66 (30.8%) were HER2-null, 53 (24.8%) HER2 ultra-low, 80 (37.4%) HER2-low, and 15 (7.0%) HER2-positive. HER2 ultra-low tumors exhibited a higher prevalence of PIK3CA mutations (39.2% vs 22.6%, p ≤ 0.05) compared to HER2-null. No significant differences were observed in TMB-high frequency or PD-L1 expression across subgroups. Immune composition differed primarily between HER2-null and HER2-expressing subgroups: HER2-ultra-low tumors showed higher B-cell infiltration, whereas HER2-null tumors were enriched in neutrophils. Transcriptomic analysis revealed upregulation of selected stemness-associated genes (NANOG, KLF4, POU5F1) and CEACAM1 in HER2-null tumors, while HER2-low and HER2-ultra-low tumors were largely similar across most molecular and immune readouts in this cohort. CONCLUSIONS: HER2-null male breast cancer appears to represent the most biologically divergent subgroup within the HER2-negative spectrum, whereas HER2-low and HER2-ultra-low tumors were largely similar in this cohort. These findings support further investigation of HER2-null disease as a distinct biological state and provide hypothesis-generating data for biomarker development in this rare population.

Male↗