American journal of physiology. Cell physiology最新文献

{"title":"AngioNet: a systems biology approach to regulation of microvascular remodeling in response to skeletal muscle activity.","authors":"Roger W P Kissane, Lukas Steuernagel, Peter G Tickle, Natalie E Doody, Michela Bonomo, Francesco Falciani, Peter K Davidsen, Stuart Egginton","doi":"10.1152/ajpcell.00397.2026","DOIUrl":"10.1152/ajpcell.00397.2026","url":null,"abstract":"<p><p>Exercise remodels skeletal muscle microvasculature, yet the transcriptional programs that distinguish functionally meaningful angiogenesis from stochastic increases in capillary number remain unclear. Here, we integrate human exercise transcriptomics with reductionist rat models to develop AngioNet, a network-based framework that resolves stimulus-specific angiogenic programs. Human endurance and resistance training datasets generated exercise mode-specific angiogenic neighborhoods, showing that canonical mediators, including VEGF-related signaling, occupy divergent network contexts across training modes. Using rat models designed to emphasize mechanical or metabolic exercise stimuli, we highlight the multitude of interactive signals capable of expanding the capillary network. However, not all microvascular expansion promotes improved oxygen delivery dynamics that translate to improvements in fatigue resistance. This functional divergence was explained by local capillary supply and distribution rather than capillary number alone. Overlaying rat transcriptomes onto AngioNet revealed that functional gains preferentially engaged extracellular matrix remodeling, vessel-matrix interaction, and coordinated endothelial-matrix programs, whereas shear-dominant stimuli produced capillary expansion without comparable matrix-remodeling network activation or improvement in fatigue resistance. Hub-set signatures, rather than individual genes, better linked transcriptional remodeling to local capillary supply area, predicted Po₂, and fatigue resistance. AngioNet therefore provides a mechanistically grounded framework to interpret heterogeneity in exercise-induced vascular adaptation and prioritize profunctional angiogenic stimuli.<b>NEW & NOTEWORTHY</b> We constructed exercise mode-specific angiogenic interaction networks (AngioNets) from endurance and resistance training human datasets. Overlapping stimulus-resolved rat transcriptomes onto these AngioNets, we showed that it is possible to promote angiogenesis through multiple stimuli, yet only a subset led to functional improvement. This divergence is explained by changes in local capillary supply, rather than gross capillary number. Across both human AngioNets, hub-set activity linked transcriptomic programs to microvascular structure, modeled tissue PO₂, and fatigue resistance.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1092-C1108"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New paradigm for old hormones: the case for 17α-estradiol as an acute therapeutic in male volumetric muscle loss.","authors":"Jarrod A Call, William T Juckett, McLane M Montgomery, Sarah M Greising","doi":"10.1152/ajpcell.00455.2026","DOIUrl":"10.1152/ajpcell.00455.2026","url":null,"abstract":"","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C960-C964"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial-Derived Exerkines Outperform Creatine Monohydrate in Enhancing Skeletal Muscle Adaptation to Exercise in Mice.","authors":"Benjamin I Burke, Jainil Daredia, Salim S El-Amouri, Lea C Range, Jeremy R Pearson, Taylor R Valentino, John J McCarthy, Yuan Wen, Ahmed Ismaeel","doi":"10.1152/ajpcell.00431.2026","DOIUrl":"10.1152/ajpcell.00431.2026","url":null,"abstract":"<p><p>We recently demonstrated that the microbial-derived exerkines (MDEs) pipecolic acid and succinate (PAS) prevent disuse-induced skeletal muscle atrophy and preserve muscle function during hindlimb immobilization in mice. Here, we investigated whether PAS also enhances exercise performance and adaptation and compared its effects with creatine monohydrate (CRE), the current gold-standard ergogenic aid for strength and power performance. Mice received vehicle (VEH), CRE, or PAS during a 7-week progressive weighted-wheel-running training protocol. Exercise performance, body composition, and skeletal muscle size and function were assessed at the conclusion of training. Both CRE and PAS enhanced high-intensity exercise performance relative to VEH, increasing running distance and time spent running during the course of the training protocol. Neither CRE nor PAS enhanced lean mass, muscle mass, or soleus myofiber cross-sectional area relative to VEH. However, PAS-treated mice exhibited greater grip strength and ex vivo soleus force production and rate of force development than both VEH and CRE. These findings demonstrate that PAS enhances strength and power adaptations to exercise beyond those achieved with CRE, identifying PAS as a promising exercise supplement and establishing MDEs as a novel class of ergogenic aids.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β1-Adrenergic antagonist monotherapy of male rabbits with ischemic HFrEF reverses sarcolemmal Na⁺-K⁺ pump inhibition and reduces lung congestion.","authors":"Natasha A S Fry, Chia-Chi Liu, Alvaro Garcia, Elisha J Hamilton, Yeon Jae Kim, Keyvan Karimi Galougahi, Henning Bundgaard, Helge H Rasmussen","doi":"10.1152/ajpcell.00177.2026","DOIUrl":"10.1152/ajpcell.00177.2026","url":null,"abstract":"<p><p>Cotreatment with angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor antagonists was obligatory, and an aldosterone antagonist was optional, in trials that established the efficacy of β1-adrenergic receptor (β1AR) antagonists in heart failure with reduced ejection fraction (HFrEF). However, with worsening HFrEF, combination treatment is often not tolerated, and patients receive β1AR antagonists only. It cannot be assumed that monotherapy is efficacious and might even be harmful because a raised myocardial cytosolic Na⁺ concentration ([Na⁺_c]) in HFrEF reduces myocardial contractility, while β1AR-coupled signaling has been widely reported to activate myocyte Na⁺-K⁺ pump-mediated Na⁺_c export in previous studies. We ligated the circumflex coronary artery of rabbits or performed sham thoracotomy. Rabbits with left ventricular ejection fraction <25% 7 days after coronary ligation were treated with the β1AR antagonist metoprolol or vehicle. Metoprolol reduced heart rate of sham-operated rabbits but not of rabbits that had coronary ligation. Metoprolol had no effect on systolic, diastolic, or mean blood pressures in either group. The primary index for heart failure, lung:body weight ratios, was ∼89% higher after coronary ligation than after sham thoracotomy, and metoprolol significantly reduced this to a ∼46% difference. The index for Na⁺-K⁺ pump function, electrogenic pump current (<i>I</i>_p), increased for myocytes from sham-operated rabbits. For myocytes from rabbits that had coronary ligation, metoprolol reversed a 63% decrease in <i>I</i>_p. Results are consistent with enhanced Na⁺-K⁺ pump-mediated Na⁺_c export in HFrEF contributing to efficacy of β1AR antagonist monotherapy independent of heart rate and afterload but do not support β1AR-coupled cyclic adenosine monophosphate (cAMP) signaling increasing cardiac Na⁺-K⁺ pump activity.<b>NEW & NOTEWORTHY</b> β1AR antagonists are frequently the only guideline-directed treatment tolerated in heart failure with reduced ejection fraction (HFrEF), and they might be deleterious because raised cytosolic [Na⁺] is harmful in HFrEF and β1AR agonists reportedly enhance myocyte Na⁺ export. Here, an antagonist reversed reduced Na⁺-K⁺ pump function of myocytes from noninfarcted myocardium in an ischemic model of HFrEF and improved pulmonary congestion, consistent with benefit of Na⁺ export but not with widely reported β1AR agonist-induced export.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C877-C887"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial DNA in necrosis-like cell death in failing hearts: evidence and mechanisms fostering damage.","authors":"Andrea Marciníková, Izabela Jarabicová, Csaba Horváth, Adriana Adameová","doi":"10.1152/ajpcell.00266.2026","DOIUrl":"10.1152/ajpcell.00266.2026","url":null,"abstract":"<p><p>Mitochondrial DNA (mtDNA) is increasingly recognized as a damage-associated molecular pattern (DAMP) that signals mitochondrial injury and the consequent pro-death molecular signature. Such mtDNA release triggers programmed necrotic pathways, specifically necroptosis and pyroptosis, both of which are central to the pathogenesis of heart failure (HF). Mechanistically, mtDNA liberated from dysfunctional mitochondria engages cytosolic nucleic acid sensors and is associated with activation of necroptotic pathways via the Z-DNA binding protein 1 (ZBP1)-receptor-interacting protein kinase 3 (RIP3)-mixed lineage kinase domain-like pseudokinase (MLKL) axis. Similarly, it can stimulate cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling to promote the de novo synthesis of pro-necroptotic cytokines. Furthermore, mtDNA release has been shown to promote pyroptosis through nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), and/or absent in melanoma 2 (AIM2) inflammasomes, amplifying a proinflammatory environment. The article examines the mechanistic cross talk between these prodeath, proinflammatory pathways with a particular emphasis on how this mechanistic cross talk drives HF. Consequently, it highlights circulating mtDNA as a key biomarker for HF severity. Finally, it posits that mtDNA-targeted therapies, such as interventions preserving mitochondrial integrity and limiting mtDNA leakage and oxidation, and interventions inhibiting mtDNA-sensing pathways, may offer a viable strategy for novel therapeutic interventions in HF.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C947-C959"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexual dimorphisms in mechanisms of pressure natriuresis.","authors":"Brandon E McFarlin, Donna L Ralph, Hermann Koepsell, Anita T Layton, Alicia A McDonough","doi":"10.1152/ajpcell.00385.2026","DOIUrl":"10.1152/ajpcell.00385.2026","url":null,"abstract":"<p><p>The renal pressure-natriuresis response defines the blood pressure set-point and maintains circulating volume. In male rats, the mechanisms involve trafficking and inactivation of renal proximal sodium transporters. Mechanisms may differ in females due to sex differences in transporters along the nephron: lower proximal and higher distal nephron salt reabsorption. We aimed to determine the impact of sex on pressure-natriuresis mechanisms. In anesthetized 8- to 10-wk-old male and female Sprague-Dawley rats, hypertension was induced by vasoconstriction (25 min), and mean arterial pressure, urine excretion, glomerular filtration rate, renal transporters' abundance (immunoblot), and subcellular location [immunohistochemistry (IHC)] were determined. A subset received 1-aminobenzotriazole (ABT) to inhibit cytochrome P450-derived arachidonic acid metabolites. At baseline, females (vs. males) exhibited lower baseline mean arterial pressure (MAP) and, during hypertension, greater sodium excretion at any given pressure, and 1.7-fold higher sodium clearance (<i>P</i> = 0.01). With hypertension, immunofluorescence revealed sex- and transporter-specific redistribution of Na/H exchanger isoform 3 (NHE3) and Na-phosphate cotransporter 2A (NaPi2) out of microvilli, and, by immunoblot, greater abundance of cortical NHE3 phosphorylated at S552 (NHE3p) in both sexes [indicating less proximal tubule (PT) reabsorption], less medullary NHE3 and Na-K-2Cl cotransporter isoform 2 (NKCC2) in females, and less distal Na-Cl cotransporter (NCC) in males. ABT provoked a leftward shift in the renal function curve in both sexes, and twofold higher natriuresis in males. Female Sprague-Dawley rats exhibit a more robust acute pressure-natriuretic response than males, facilitated by baseline sex differences in renal transporter patterns and reduced medullary NHE3 and NKCC2. These female-specific responses augment the pressure-natriuresis response, which may contribute to their lower baseline blood pressure.<b>NEW & NOTEWORTHY</b> Three discoveries contribute to understanding sex differences in blood pressure set-point: <i>1</i>) females exhibit a greater natriuresis to acute hypertension (aHTN) than males; <i>2</i>) aHTN provokes sex-specific molecular adaptations along the nephron: proximal NHE3 and NaPi2 redistribute in both sexes; medullary NHE3 and NKCC2 abundance are reduced in females, distal NCC abundance is reduced in males; <i>3</i>) inhibition of arachidonic acid metabolites shifts renal function curves leftward in both sexes, and augments natriuresis in males.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C965-C981"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel role for TRPV1 in macrophage giant cell formation.","authors":"Karunakaran R Sankaran, Mohammad I Khan, Shaik O Rahaman","doi":"10.1152/ajpcell.90011.2026","DOIUrl":"10.1152/ajpcell.90011.2026","url":null,"abstract":"<p><p>Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel with high permeability to Ca²⁺ and is best known for its roles in sensory signaling. However, its function in immune cell biology, particularly in macrophage fusion, remains unknown. Cell fusion is a critical process in both physiological and pathological contexts, including development, tissue remodeling, and the foreign body response (FBR) to implanted biomaterials. During FBR, macrophages undergo fusion to form multinucleated foreign body giant cells (FBGCs), which contribute to implant degradation and fibrotic encapsulation. Here, we identify TRPV1 as a key regulator of macrophage multinucleation and FBGC formation. We demonstrate that TRPV1 is endogenously expressed in bone marrow-derived macrophages (BMDMs) and is upregulated in response to fusogenic cytokines and inflammatory stimuli. Functionally, TRPV1 promotes matrix stiffness-dependent macrophage adhesion and spreading, indicating a role in mechanosensitive signaling. We show that TRPV1 is required for efficient macrophage fusion under both cytokine-driven and matrix stiffness-mediated conditions. Mechanistically, TRPV1 links extracellular mechanical cues and cytokine signaling to cytoskeletal remodeling, facilitating the actin reorganization necessary for cell fusion. Importantly, TRPV1 deficiency does not alter TRPV4-mediated Ca²⁺ signaling, demonstrating that TRPV1 operates independently of TRPV4, a known mechanosensitive channel implicated in FBR and FBGC formation. Collectively, these findings suggest TRPV1 as a previously unrecognized mechanosensitive regulator of macrophage fusion and FBGC formation. This work provides new insight into the molecular mechanisms governing FBR and identifies TRPV1 as a potential therapeutic target for improving biomaterial biocompatibility and mitigating fibrosis.<b>NEW & NOTEWORTHY</b> This study identifies TRPV1 as a novel regulator of macrophage fusion and giant cell formation. TRPV1 integrates matrix stiffness and fusogenic cytokine signals to promote cytoskeletal remodeling and multinucleation while functioning independently of TRPV4 channel. These findings reveal TRPV1 as a promising therapeutic target for limiting foreign body responses and improving the long-term performance of implanted biomaterials.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C999-C1009"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"O₂-sensing and HIF regulation: from oxygen homeostasis to tumor-associated immune responses.","authors":"Vivienne Schneider, Joachim Fandrey, Sandra Winning","doi":"10.1152/ajpcell.00185.2026","DOIUrl":"10.1152/ajpcell.00185.2026","url":null,"abstract":"<p><p>Oxygen is needed to generate adenosine triphosphate (ATP) via aerobic respiration in mitochondria. Hypoxia-when the tissue's oxygen demand exceeds its supply-characterizes not only sites of acute inflammation but also many tumors and their microenvironment. But even then, (immune) cells must ensure sufficient ATP synthesis. Under hypoxic conditions, hypoxia-inducible factors (HIFs) are capable of adapting cellular metabolism by induction of hundreds of target genes that, among others, regulate glycolysis, cell survival, and angiogenesis. This may hold true for immune cells under homeostatic conditions when they are forced to fight against pathogens and for tumor cells when the activation of HIFs enables tumor cells to survive in oxygen-deficient tissues. In addition, HIF activation in many tumors promotes the creation of an immunosuppressive tumor microenvironment that prevents immune cells from effectively fighting the tumor. Therefore, promising approaches have been made in the combination of immune therapies with HIF inhibition. In this review, we highlight that a better understanding of the role of hypoxic adaptation requires considering the HIF stabilization patterns of tumor type, tumor stage, and the immune cells within the tumor microenvironment to optimize therapeutic efficacy.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C849-C863"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross talk between SARS-CoV-2 and the angiotensin system: clinical implications.","authors":"Safa Kinaneh, Shadi Hamoud, Yara Knany, Samuel N Heyman, Zaid Abassi","doi":"10.1152/ajpcell.00786.2025","DOIUrl":"10.1152/ajpcell.00786.2025","url":null,"abstract":"<p><p>Angiotensin-converting enzyme 2 (ACE2), serving as a receptor to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a key player in renin-angiotensin-aldosterone system (RAAS). Consequent ACE2 depletion disrupts the balance between the angiotensin II (Ang-II)/angiotensin 1 receptor (AT1R) and angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) arms of the angiotensin system, promoting intense inflammation. A cross talk existing between the angiotensin system and ACE2/spike proteins that may affect infection severity, with potential therapeutic implications. Evaluating such potential interactions and their relevance to the severity of coronavirus disease 2019 (COVID-19), which is directly affected by ACE2 abundance or indirectly by RAAS axis dysregulation. The intensity of SARS-CoV-2 infection was assessed using a cell-to-cell fusion assay, and AT1R activation was assessed using AT1R-Tango approach. We demonstrate the critical function of ACE2 in mitigating AT1R activation, which is disrupted following SARS-CoV-2 infection. Moreover, we show that the spike protein indirectly intensifies AT1R activation. Beyond its established role in activating MasR, Ang 1-7 was found to function as a biased agonist for AT1R, without altering ACE2 levels or affecting SARS-CoV-2 entry. In contrast, AVE0991, a MasR agonist, was observed to increase ACE2 levels and enhance SARS-CoV-2 infection. Angiotensin receptor blockers (ARBs) effectively inhibited AT1R activity and had minimal impact on viral entry. Our data support the likelihood that AT1R blockers (ARBs) may be effective in managing COVID-19 since they inhibit AT1R activation and its deleterious subsequent effects, with no impact on SARS-CoV-2 entry. By contrast, MasR and its agonist AVE0991, by increasing ACE2 levels, may restore RAAS physiological balance, but facilitate host cell invasion by SARS-CoV-2.<b>NEW & NOTEWORTHY</b> This study characterizes the interaction between the angiotensin system and angiotensin-converting enzyme 2 (ACE2)/spike proteins and its significance for coronavirus disease 2019 (COVID-19) severity. Using a cell-to-cell fusion assay and angiotensin 1 receptor (AT1R) activation assessment via the AT1R-Tango approach, we reveal a crucial role of ACE2 in attenuating AT1R activation. Furthermore, the data indicate that the spike protein indirectly amplifies AT1R activation. In addition, angiotensin 1-7 (Ang 1-7) was identified to act not only as Mas receptor (MasR) agonist, but also as a biased agonist for AT1R.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C982-C998"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular cues and cellular conversations: the molecular choreography of embryo implantation.","authors":"Janice K Jeschke, Verena Nordhoff, Martin Götte, Konstantina Kyriakopoulou","doi":"10.1152/ajpcell.00048.2026","DOIUrl":"10.1152/ajpcell.00048.2026","url":null,"abstract":"<p><p>Infertility affects millions of people globally with recent statistics indicating that one in six adults is experiencing reproductive challenges at some point. For female infertility in particular, the global health burden is continuously intensifying with significant disparities across countries. Female infertility has a complex multifactorial etiology, and understanding the underlying mechanisms is crucial to reduce the health burden and enhance patient well-being. For a pregnancy, successful embryo implantation is a pivotal step, requiring precise spatiotemporal synchronization between a competent blastocyst and a receptive endometrium during the window of implantation (WOI). This review provides an overview of recent developments around the molecular and clinical aspects of this process, with a specific focus on the extracellular microenvironmental cues and maternal-embryo interaction. Specifically, we detail the extensive extracellular matrix (ECM) remodeling that facilitates embryo adhesion and invasion while shedding light on microRNAs as signaling and communication mediators that govern cell-cell and maternal-fetal interactions. Finally, we examine current limitations in the clinical assessment of receptivity and discuss future perspectives for noninvasive biomarkers and possibilities for more personalized solutions in assisted reproduction.</p>","PeriodicalId":7585,"journal":{"name":"American journal of physiology. Cell physiology","volume":" ","pages":"C1047-C1060"},"PeriodicalIF":5.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}