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Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 307-323页

作者： Xufeng FU Hang HAN Hong YANG Bo XU Wenjie DAI Ling LIU Tiantian HE Xing DU Xiuying PEI Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China Key Laboratory of reproduction and Genetics in Ningxia Ningxia Medical UniversityYinchuan 750004China

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain *** this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in ***,whole-body imaging found that PS-NPs accumulated in the testes of ***,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were *** oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were *** spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP *** phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by ***,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive *** study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

关键词： Polvstyrene nanoplastics(PS-NPs) Reproductive toxicity Ferroptosis Nuclear factor ervthroid 2-related factor 2(Nrf2)

Dynamic transcriptome profiles and novel markers in bovine spermatogenesis revealed by single-cell sequencing

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Journal of Integrative Agriculture 2024年第7期23卷 2362-2378页

作者： Yuan Gao Fuxia Bai Qi Zhang Xiaoya An Zhaofei Wang Chuzhao Lei Ruihua Dang Key Laboratory of Animal Genetics Breeding and Reproduction of Shaanxi ProvinceCollege of Animal Science and TechnologyNorthwest A&F UniversityYangling 712100China College of Life sciences Northwestern Polytechnical UniversityXi’an 710072China

Testicular development is an important biological process in male and requires interaction between the male germ cells and somatic ***,the mechanisms of testicular development in livestock,particularly in cattle,are poorly ***,cellular heterogeneity hinders the profiling of different cell types at different developmental *** this study,we first performed a single-cell transcriptomic study of the bovine testis development during puberty by using 10×genomics single-cell RNA sequencing(scRNA-seq).By collecting the scRNA-seq data from 11,083 cells from prepubertal and pubertal bovine testes,a high-resolution scRNA-seq atlas was described,identifying 9 somatic and 13 spermatogenic *** also distinguished several stage-specific marker genes for bovine germ cells and somatic cells,such as GRAF2 and MORC1 for SSC(spermatogonial stem cells),HJURP and TCF19 for differentiating spermatogonia,ARSE for immature Sertoli,CLEC12B for mature Sertoli,LOC112441470 for *** conclusion,we have examined the transcription levels and constructed the single-cell developmental maps of germ cells and somatic cells during testicular development in Angus *** datasets provided new insights into spermatogenesis and testicular somatic cell development in cattle.

关键词： scRNA-seq cattle spermatogenesis testis development

RNA m6A dynamic modification mediated by nucleuslocalized FTO is involved in follicular reserve

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Zoological Research 2024年第2期45卷 415-428页

作者： Jiao-Na Zhang Rui-Ting Wang Francesca-Gioia Klinger Shun-Feng Cheng Wei Shen Xiao-Feng Sun College of Life sciences Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of ShandongQingdao Agricultural UniversityQingdaoShandong 266109China Department of Biomedicine and Prevention University of Rome Tor VergataRome 00133Italy

In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and *** fat-mass and obesity-associated protein(FTO)catalyzes RNA demethylation and plays a critical role in various physiological and pathological *** research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles,with an inverse relationship observed for m6A levels and nuclear-localized FTO *** of Fto small interfering RNA(si RNA)altered the expression of genes related to cell proliferation,hormone regulation,and cell chemotaxis,and affected RNA alternative *** of the full-length Fto gene led to changes in m6A levels,alternative splicing of Cdk5,cell proliferation,cell cycle progression,and proportion of primordial ***,overexpression of Fto lacking a nuclear localization signal(NLS)did not significantly alter m6A levels or primordial follicle *** findings suggest that FTO,localized in the nucleus but not in the cytoplasm,regulates RNA m6A demethylation and plays a role in cell proliferation,cell cycle progression,and primordial follicle *** results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.

关键词： m6A FTO Ovary Primordial follicle assembly Alternative splicing

Therapeutic advances in atrial fibrillation based on animal models

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第2期25卷 135-152页

作者： Qian GONG Xuan LE Pengcheng YU Lenan ZHUANG Institute of Genetics and reproduction College of Animal SciencesZhejiang UniversityHangzhou310058China Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of CardiologySir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou310016China

Atrial fibrillation(AF)is the most prevalent sustained cardiac arrhythmia among humans,with its incidence increasing significantly with *** the high frequency of AF in clinical practice,its etiology and management remain *** develop effective treatment strategies,it is imperative to comprehend the underlying mechanisms of AF;therefore,the establishment of animal models of AF is vital to explore its *** spontaneous AF is rare in most animal species,several large animal models,particularly those of pigs,dogs,and horses,have proven as invaluable in recent years in advancing our knowledge of AF pathogenesis and developing novel therapeutic *** review aims to provide a comprehensive discussion of various animal models of AF,with an emphasis on the unique features of each model and its utility in AF research and *** data summarized in this review provide valuable insights into the mechanisms of AF and can be used to evaluate the efficacy and safety of novel therapeutic interventions.

关键词： Atrial fibrillation Animal model Therapeutic

Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress

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Journal of Integrative Medicine 2024年第4期22卷 493-502页

作者： Qian-zhuo Liu Hui Han Xin-ru Fang Lu-yao Wang Dan Zhao Miao-zhu Yin Nian Zhang Peng-yu Jiang Zhi-hui Ji Li-min Wu Department of Neurology the First Affiliated Hospital of Anhui University of Chinese MedicineHefei 230031Anhui ProvinceChina Center for reproduction and Genetics the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230031Anhui ProvinceChina

Objective:Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for ***:Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione(GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) ***:Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine,a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron,Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4)expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) ***:Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.

关键词： Berberine Hepatolenticular degeneration Copper deposition Ferroptosis Endoplasmic reticulum stress

Sperm function, mitochondrial activity and in vivo fertility are associated to their mitochondrial DNA content in pigs

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1550-1558页

作者： Marc Llavanera Yentel Mateo‑Otero Estel Vinolas‑Verges Sergi Bonet Marc Yeste Unit of Cell Biology Department of BiologyFaculty of SciencesUniversity of GironaGirona ES‑17003Spain Biotechnology of Animal and Human reproduction(TechnoSperm) Institute of Food and Agricultural TechnologyUniversity of GironaGirona ES‑17003Spain Catalan Institution for Research and Advanced Studies(ICREA) Barcelona ES‑08010Spain

Background Despite their low abundance in sperm, mitochondria have diverse functions in this cell type, includ-ing energy production, signalling and calcium regulation. In humans, sperm mitochondrial DNA content(mtDNAc) has been reported to be negatively linked to sperm function and fertility. Yet, the association between mtDNAc and sperm function in livestock remains unexplored. For this reason, this study aimed to shed some light on the link between mtDNAc and sperm function and fertilising potential in pigs. A qPCR method for mtDNAc quantification was optimised for pig sperm, and the association of this parameter with sperm motility, kinematics, mitochondrial activity, and fertility was subsequently *** First, the q PCR method was found to be sensitive and efficient for mtDNAc quantification in pig sperm. By using this technique, mtDNAc was observed to be associated to sperm motility, mitochondrial activity and in vivo, but not in vitro, fertility outcomes. Specifically, sperm with low mtDNAc were seen to exhibit greater motility but decreased mitochondrial activity and intracellular reactive oxygen species. Interestingly, samples with lower mtD-NAc showed higher conception and farrowing rates, but similar in vitro fertilisation rates and embryo development, when compared to those with greater *** These findings enrich our comprehension of the association of mtDNAc with sperm biology, and lay the foundation for future research into employing this parameter as a molecular predictor for sperm function and fer-tility in livestock.

关键词： Fertility Mitochondria Motility mtDNA copy number qPCR Sperm

Polyoxidovanadates a new therapeutic alternative for neurodegenerative and aging diseases

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Neural Regeneration Research 2024年第3期19卷 571-577页

作者： Sonia Irais Gonzalez-Cano Gonzalo Flores Jorge Guevara Julio Cesar Morales-Medina Samuel Treviño Alfonso Diaz Faculty of Chemical sciences Benemerita Autonomous University of PueblaPueblaMexico Institute of Physiology Benemerita Autonomous University of PueblaPueblaMexico Department of Biochemistry Faculty of MedicineNational Autonomous University of MexicoMexico CityMexico Animal reproduction Research Center CINVESTAV-Autonomous University of TlaxcalaTlaxcalaMexico

Aging is a natural phenomenon characterized by a progressive decline in physiological integrity,leading to a deterioration of cognitive function and increasing the risk of suffering from chronic-degenerative diseases,including cardiovascular diseases,osteoporosis,cancer,diabetes,and *** is considered the major risk factor for Parkinson’s and Alzheimer’s disease ***,diabetes and insulin resistance constitute additional risk factors for developing neurodegenerative ***,no treatment can effectively reverse these neurodegenerative ***,some antidiabetic drugs have opened the possibility of being used against neurodegenerative *** the previous framework,Vanadium species have demonstrated a notable antidiabetic *** research group evaluated polyoxidovanadates such as decavanadate and metforminium-decavanadate with preventive and corrective activity on neurodegeneration in brain-specific areas from rats with metabolic *** results suggest that these polyoxidovanadates induce neuronal and cognitive restoration *** review aims to describe the therapeutic potential of polyoxidovanadates as insulin-enhancer agents in the brain,constituting a therapeutic alternative for aging and neurodegenerative diseases.

关键词： Alzheimer’s disease antidiabetic brain cognition diabetes insulin neurodegeneration neuroinflammation oxidative stress Vanadium species

Rare variants in FANCJ induce premature ovarian insufficiency in humans and mice

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Journal of Genetics and Genomics 2024年第2期51卷 252-255页

作者： Xi Yang Shuting Ren Jialin Yang Yuncheng Pan Zixue Zhou Qing Chen Yunzheng Fang Lingyue Shang Feng Zhang Xiaojin Zhang Yanhua Wu State Key Laboratory of Genetic Engineering at School of Life sciences Human Phenome InstituteObstetrics and Gynecology HospitalFudan UniversityShanghai 200438China Obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentState Key Laboratory of Genetic Engineering at School of Life SciencesFudan UniversityShanghai 200011China Human Phenome Institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Obstetrics and Gynecology Hospital Institute of Reproduction and DevelopmentFudan UniversityShanghai 200011China State Key Laboratory of Genetic Engineering at School of Life sciences Obstetrics and Gynecology HospitalFudan UniversityShanghai 200438China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China

Premature ovarian insufficiency(POI)is a severe female reproductive disorder that affects 1%of women in general populations(European Society for Human reproduction and Embryology[ESHRE]Guideline Group on POI et al.,2016).An increasing prevalence up to 3.7%has been reported in a recent meta-analysis(Golezar et al.,2019).POl can lead to infertility or subfertility,as well as a range of complex complications suffering multi-organ systems,seriously threatening women's health and reducing the life *** contrast,POl is a representative heterogeneous disease with multiple *** more than 70 causative POI genes have been identified,the etiology of more than half of the POI patients is still ambiguous(Jiao et al.,2018).Unreported POI causative genes,therefore,remain to be identified.

关键词： insufficiency fertility

A mutation in TBXT causes congenital vertebral malformations in humans and mice

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Journal of Genetics and Genomics 2024年第4期51卷 433-442页

作者： Shuxia Chen Yunping Lei Yajun Yang Chennan Liu Lele Kuang Li Jin Richard HFinnell Xueyan Yang Hongyan Wang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic Engineering at School of Life SciencesKey Laboratory of Reproduction Regulation of NPFPCInstitute of Reproduction and DevelopmentFudan UniversityShanghai 200438China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Center for Precision Environmental Health Department of Molecular and Cellular BiologyBaylor College of MedicineHoustonTX 77030USA MOE Key Laboratory of Contemporary Anthropology School of Life SciencesFudan UniversityShanghai 200438China Department of Assisted reproduction Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Children’s Hospital Fudan University399 Wanyuan RoadShanghai 201102China

T-box transcription factor T(TBXT;T)is required for mesodermal formation and axial skeletal *** it has been extensively studied in various model organisms,human congenital vertebral malformations(CVMs)involving T are not well ***,we report a family with 15 CVM patients distributed across 4 *** affected individuals carry a heterozygous mutation,T c.596A>G(p.Q199R),which is not found in unaffected family members,indicating co-segregation of the genotype and *** vitro assays show that T p.Q199R increases the nucleocytoplasmic ratio and enhances its DNA-binding affinity,but reduces its transcriptional activity compared to the *** determine the pathogenicity of this mutation in vivo,we generated a Q199R knock-in mouse model that recapitulates the human CVM *** heterozygous Q199R mice show subtle kinked or shortened tails,while homozygous mice exhibit tail filaments and severe vertebral ***,we show that the Q199R mutation in T causes CVM in humans and mice,providing previously unreported evidence supporting the function of T in the genetic etiology of human CVM.

关键词： Congenital vertebral malformation TBXT T gene Loss-of-function mutation