Biological Research最新文献

{"title":"Chrysin-loaded PEGylated liposomes protect against alloxan-induced diabetic neuropathy in rats: the interplay between endoplasmic reticulum stress and autophagy.","authors":"Mahran Mohamed Abd El-Emam, Amany Behairy, Mahmoud Mostafa, Tarek Khamis, Noura M S Osman, Amira Ebrahim Alsemeh, Mohamed Fouad Mansour","doi":"10.1186/s40659-024-00521-1","DOIUrl":"10.1186/s40659-024-00521-1","url":null,"abstract":"<p><strong>Background: </strong>Diabetic neuropathy (DN) is recognized as a significant complication arising from diabetes mellitus (DM). Pathogenesis of DN is accelerated by endoplasmic reticulum (ER) stress, which inhibits autophagy and contributes to disease progression. Autophagy is a highly conserved mechanism crucial in mitigating cell death induced by ER stress. Chrysin, a naturally occurring flavonoid, can be found abundantly in honey, propolis, and various plant extracts. Despite possessing advantageous attributes such as being an antioxidant, anti-allergic, anti-inflammatory, anti-fibrotic, and anticancer agent, chrysin exhibits limited bioavailability. The current study aimed to produce a more bioavailable form of chrysin and discover how administering chrysin could alter the neuropathy induced by Alloxan in male rats.</p><p><strong>Methods: </strong>Chrysin was formulated using PEGylated liposomes to boost its bioavailability and formulation. Chrysin PEGylated liposomes (Chr-PLs) were characterized for particle size diameter, zeta potential, polydispersity index, transmission electron microscopy, and in vitro drug release. Rats were divided into four groups: control, Alloxan, metformin, and Chr-PLs. In order to determine Chr- PLs' antidiabetic activity and, by extension, its capacity to ameliorate DN, several experiments were carried out. These included measuring acetylcholinesterase, fasting blood glucose, insulin, genes dependent on autophagy or stress in the endoplasmic reticulum, and histopathological analysis.</p><p><strong>Results: </strong>According to the results, the prepared Chr-PLs exhibited an average particle size of approximately 134 nm. They displayed even distribution of particle sizes. The maximum entrapment efficiency of 90.48 ± 7.75% was achieved. Chr-PLs effectively decreased blood glucose levels by 67.7% and elevated serum acetylcholinesterase levels by 40% compared to diabetic rats. Additionally, Chr-PLs suppressed the expression of ER stress-related genes (ATF-6, CHOP, XBP-1, BiP, JNK, PI3K, Akt, and mTOR by 33%, 39.5%, 32.2%, 44.4%, 40.4%, 39.2%, 39%, and 35.9%, respectively). They also upregulated the miR-301a-5p expression levels by 513% and downregulated miR-301a-5p expression levels by 65%. They also boosted the expression of autophagic markers (AMPK, ULK1, Beclin 1, and LC3-II by 90.3%, 181%, 109%, and 78%, respectively) in the sciatic nerve. The histopathological analysis also showed that Chr-PLs inhibited sciatic nerve degeneration.</p><p><strong>Conclusion: </strong>The findings suggest that Chr-PLs may be helpful in the protection against DN via regulation of ER stress and autophagy.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11232158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lead and calcium crosstalk tempted acrosome damage and hyperpolarization of spermatozoa: signaling and ultra-structural evidences.","authors":"Rajkumar Singh Yadav, Bhawna Kushawaha, Rahul Dhariya, Dilip Kumar Swain, Brijesh Yadav, Mukul Anand, Priyambada Kumari, Pradeep Kumar Rai, Dipty Singh, Sarvajeet Yadav, Satish Kumar Garg","doi":"10.1186/s40659-024-00517-x","DOIUrl":"10.1186/s40659-024-00517-x","url":null,"abstract":"<p><strong>Background: </strong>Exposure of humans and animals to heavy metals is increasing day-by-day; thus, lead even today remains of significant public health concern. According to CDC, blood lead reference value (BLRV) ranges from 3.5 µg/dl to 5 μg/dl in adults. Recently, almost 2.6% decline in male fertility per year has been reported but the cause is not well established. Lead (Pb²⁺) affects the size of testis, semen quality, and secretory functions of prostate. But the molecular mechanism(s) of lead toxicity in sperm cells is not clear. Thus, present study was undertaken to evaluate the adverse effects of lead acetate at environmentally relevant exposure levels (0.5, 5, 10 and 20 ppm) on functional and molecular dynamics of spermatozoa of bucks following in vitro exposure for 15 min and 3 h.</p><p><strong>Results: </strong>Lead significantly decreased motility, viable count, and motion kinematic patterns of spermatozoa like curvilinear velocity, straight-line velocity, average path velocity, beat cross frequency and maximum amplitude of head lateral displacement even at 5 ppm concentration. Pb²⁺ modulated intracellular cAMP and Ca²⁺ levels in sperm cells through L-type calcium channels and induced spontaneous or premature acrosome reaction (AR) by increasing tyrosine phosphorylation of sperm proteins and downregulated mitochondrial transmembrane potential. Lead significantly increased DNA damage and apoptosis as well. Electron microscopy studies revealed Pb²⁺ -induced deleterious effects on plasma membrane of head and acrosome including collapsed cristae in mitochondria.</p><p><strong>Conclusions: </strong>Pb²⁺ not only mimics Ca²⁺ but also affects cellular targets involved in generation of cAMP, mitochondrial transmembrane potential, and ionic exchange. Lead seems to interact with Ca²⁺ channels because of charge similarity and probably enters the sperm cell through these channels and results in hyperpolarization. Our findings also indicate lead-induced TP and intracellular Ca²⁺ release in spermatozoa which in turn may be responsible for premature acrosome exocytosis which is essential feature of capacitation for fertilization. Thus, lead seems to reduce the fertilizing capacity of spermatozoa even at 0.5 ppm concentrations.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11225213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Tridax procumbens flavonoids promote osteoblast differentiation and bone formation.","authors":"Md Abdullah Al Mamun, Mohammad Jakir Hosen, Kamrul Islam, Amina Khatun, M Masihul Alam, Md Abdul Alim Al-Bari","doi":"10.1186/s40659-024-00525-x","DOIUrl":"10.1186/s40659-024-00525-x","url":null,"abstract":"","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular hydrogen promotes retinal vascular regeneration and attenuates neovascularization and neuroglial dysfunction in oxygen-induced retinopathy mice.","authors":"Yatu Guo, Jiahui Qin, Ruiqiang Sun, Peng Hao, Zhixin Jiang, Yuchuan Wang, Zhiqi Gao, Huan Zhang, Keliang Xie, Wei Zhang","doi":"10.1186/s40659-024-00515-z","DOIUrl":"10.1186/s40659-024-00515-z","url":null,"abstract":"<p><strong>Background: </strong>Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H₂) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H₂ provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H₂ on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice.</p><p><strong>Methods: </strong>In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2-/-) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H₂) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H₂ under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining.</p><p><strong>Results: </strong>Our results indicate that 3-4% H₂ does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H₂ prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H₂ inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H₂ plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H₂ promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreove","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise reduces physical alterations in a rat model of fetal alcohol spectrum disorders.","authors":"Ronald Vargas-Foitzick, Bayron García-Ordenes, Donovan Iratchet, Angie Acuña, Spencer Alcayaga, Cristian Fernández, Karla Toledo, Marianela Rodríguez, Carolina Naranjo, René Bustamante, Paola A Haeger","doi":"10.1186/s40659-024-00520-2","DOIUrl":"10.1186/s40659-024-00520-2","url":null,"abstract":"<p><strong>Background: </strong>Prenatal alcohol exposure (PAE) has serious physical consequences for children such as behavioral disabilities, growth disorders, neuromuscular problems, impaired motor coordination, and decreased muscle tone. However, it is not known whether loss of muscle strength occurs, and which interventions will effectively mitigate physical PAE impairments. We aimed to investigate whether physical alteration persists during adolescence and whether exercise is an effective intervention.</p><p><strong>Results: </strong>Using paradigms to evaluate different physical qualities, we described that early adolescent PAE animals have significant alterations in agility and strength, without alterations in balance and coordination compared to CTRL animals. We evaluated the effectiveness of 3 different exercise protocols for 4 weeks: Enrichment environment (EE), Endurance exercise (EEX), and Resistance exercise (REX). The enriched environment significantly improved the strength in the PAE group but not in the CTRL group whose strength parameters were maintained even during exercise. Resistance exercise showed the greatest benefits in gaining strength, and endurance exercise did not.</p><p><strong>Conclusion: </strong>PAE induced a significant decrease in strength compared to CTRL in PND21. Resistance exercise is the most effective to reverse the effects of PAE on muscular strength. Our data suggests that individualized, scheduled, and supervised training of resistance is more beneficial than endurance or enriched environment exercise for adolescents FASD.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of protein tyrosine phosphatase receptor delta PTPRD increases the number of cortical neurons, impairs synaptic function and induces autistic-like behaviors in adult mice.","authors":"Bastián I Cortés, Rodrigo C Meza, Carlos Ancatén-González, Nicolás M Ardiles, María-Ignacia Aránguiz, Hideaki Tomita, David R Kaplan, Francisca Cornejo, Alexia Nunez-Parra, Pablo R Moya, Andrés E Chávez, Gonzalo I Cancino","doi":"10.1186/s40659-024-00522-0","DOIUrl":"10.1186/s40659-024-00522-0","url":null,"abstract":"<p><strong>Background: </strong>The brain cortex is responsible for many higher-level cognitive functions. Disruptions during cortical development have long-lasting consequences on brain function and are associated with the etiology of brain disorders. We previously found that the protein tyrosine phosphatase receptor delta Ptprd, which is genetically associated with several human neurodevelopmental disorders, is essential to cortical brain development. Loss of Ptprd expression induced an aberrant increase of excitatory neurons in embryonic and neonatal mice by hyper-activating the pro-neurogenic receptors TrkB and PDGFRβ in neural precursor cells. However, whether these alterations have long-lasting consequences in adulthood remains unknown.</p><p><strong>Results: </strong>Here, we found that in Ptprd+/- or Ptprd-/- mice, the developmental increase of excitatory neurons persists through adulthood, affecting excitatory synaptic function in the medial prefrontal cortex. Likewise, heterozygosity or homozygosity for Ptprd also induced an increase of inhibitory cortical GABAergic neurons and impaired inhibitory synaptic transmission. Lastly, Ptprd+/- or Ptprd-/- mice displayed autistic-like behaviors and no learning and memory impairments or anxiety.</p><p><strong>Conclusions: </strong>These results indicate that loss of Ptprd has long-lasting effects on cortical neuron number and synaptic function that may aberrantly impact ASD-like behaviors.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of astroglial hemichannels prevents synaptic transmission decline during spreading depression.","authors":"Juan E Tichauer, Matías Lira, Waldo Cerpa, Juan A Orellana, Juan C Sáez, Maximiliano Rovegno","doi":"10.1186/s40659-024-00519-9","DOIUrl":"10.1186/s40659-024-00519-9","url":null,"abstract":"<p><strong>Background: </strong>Spreading depression (SD) is an intriguing phenomenon characterized by massive slow brain depolarizations that affect neurons and glial cells. This phenomenon is repetitive and produces a metabolic overload that increases secondary damage. However, the mechanisms associated with the initiation and propagation of SD are unknown. Multiple lines of evidence indicate that persistent and uncontrolled opening of hemichannels could participate in the pathogenesis and progression of several neurological disorders including acute brain injuries. Here, we explored the contribution of astroglial hemichannels composed of connexin-43 (Cx43) or pannexin-1 (Panx1) to SD evoked by high-K⁺ stimulation in brain slices.</p><p><strong>Results: </strong>Focal high-K⁺ stimulation rapidly evoked a wave of SD linked to increased activity of the Cx43 and Panx1 hemichannels in the brain cortex, as measured by light transmittance and dye uptake analysis, respectively. The activation of these channels occurs mainly in astrocytes but also in neurons. More importantly, the inhibition of both the Cx43 and Panx1 hemichannels completely prevented high K⁺-induced SD in the brain cortex. Electrophysiological recordings also revealed that Cx43 and Panx1 hemichannels critically contribute to the SD-induced decrease in synaptic transmission in the brain cortex and hippocampus.</p><p><strong>Conclusions: </strong>Targeting Cx43 and Panx1 hemichannels could serve as a new therapeutic strategy to prevent the initiation and propagation of SD in several acute brain injuries.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11167948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Conformational characterization of the mammalian-expressed SARS-CoV-2 recombinant receptor binding domain, a COVID-19 vaccine.","authors":"Leina Moro-Pérez, Tammy Boggiano-Ayo, Sum Lai Lozada-Chang, Olga Lidia Fernández-Saiz, Beatriz Perez-Masson, Kathya Rashida de la Luz, Jose Alberto Gómez-Pérez","doi":"10.1186/s40659-024-00514-0","DOIUrl":"10.1186/s40659-024-00514-0","url":null,"abstract":"","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The current insights of mitochondrial hormesis in the occurrence and treatment of bone and cartilage degeneration.","authors":"Wacili Da, Quan Chen, Bin Shen","doi":"10.1186/s40659-024-00494-1","DOIUrl":"10.1186/s40659-024-00494-1","url":null,"abstract":"<p><p>It is widely acknowledged that aging, mitochondrial dysfunction, and cellular phenotypic abnormalities are intricately associated with the degeneration of bone and cartilage. Consequently, gaining a comprehensive understanding of the regulatory patterns governing mitochondrial function and its underlying mechanisms holds promise for mitigating the progression of osteoarthritis, intervertebral disc degeneration, and osteoporosis. Mitochondrial hormesis, referred to as mitohormesis, represents a cellular adaptive stress response mechanism wherein mitochondria restore homeostasis and augment resistance capabilities against stimuli by generating reactive oxygen species (ROS), orchestrating unfolded protein reactions (UPRmt), inducing mitochondrial-derived peptides (MDP), instigating mitochondrial dynamic changes, and activating mitophagy, all prompted by low doses of stressors. The varying nature, intensity, and duration of stimulus sources elicit divergent degrees of mitochondrial stress responses, subsequently activating one or more signaling pathways to initiate mitohormesis. This review focuses specifically on the effector molecules and regulatory networks associated with mitohormesis, while also scrutinizing extant mechanisms of mitochondrial dysfunction contributing to bone and cartilage degeneration through oxidative stress damage. Additionally, it underscores the potential of mechanical stimulation, intermittent dietary restrictions, hypoxic preconditioning, and low-dose toxic compounds to trigger mitohormesis, thereby alleviating bone and cartilage degeneration.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The crucial role of HFM1 in regulating FUS ubiquitination and localization for oocyte meiosis prophase I progression in mice.","authors":"Chenyi Zhong, Huiyuan Wang, Xiong Yuan, Yuheng He, Jing Cong, Rui Yang, Wenjie Ma, Li Gao, Chao Gao, Yugui Cui, Jie Wu, Rongrong Tan, Danhua Pu","doi":"10.1186/s40659-024-00518-w","DOIUrl":"10.1186/s40659-024-00518-w","url":null,"abstract":"<p><strong>Background: </strong>Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes.</p><p><strong>Results: </strong>The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1.</p><p><strong>Conclusions: </strong>These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11140966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}