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RNF187 governs the maintenance of mouse GC-2 cell development by facilitating histone H3 ubiquitination at K57/80

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Asian Journal of Andrology 2024年第3期26卷 272-281页

作者： Bing-Ya Xu Xiang-Ling Yu Wen-Xin Gao Ting-Ting Gao Hao-Yue Hu Tian-Tian Wu Cong Shen Xiao-Yan Huang Bo Zheng Yi-Bo Wu Human Reproductive and Genetic Center Affiliated Hospital of Jiangnan UniversityWuxi 214122China State Key laboratory of Reproductive Medicine Department of Histology and EmbryologySchool of Basic Medical SciencesNanjing Medical UniversityNanjing 211166China Changzhou Maternal and Child Health Care Hospital Changzhou Medical CenterNanjing Medical UniversityChangzhou 213000China State Key laboratory of Reproductive Medicine Center for Reproduction and GeneticsSuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversitySuzhou 215002China

RING finger 187(RNF187),a ubiquitin-ligating(E3)enzyme,plays a crucial role in the proliferation of cancer ***,it remains unclear whether RNF187 exhibits comparable functionality in the development of germline *** investigate thepotential involvement of RNF187 in germ cell development,we conducted interference and overexpression assays using GC-2 cells,a mouse spermatocyte-derived cell *** findings reveal that the interaction between RNF187 and histone H3 increases theviability,proliferation,and migratory capacity of GC-2 ***,we provide evidence demonstrating that RNF187 interactswith H3 and mediates the ubiquitination of H3 at lysine 57(K57)or lysine 80(K80),directly or indirectly resulting in increasedcellular *** is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediatinghistone H3 ubiquitination,thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of *** discoveries provide a new theoretical foundation for further comprehensive investigations into the functionof RNF187 in the reproductive system.

关键词： GC-2 cell histone H3 RNF187 ubiquitination

Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis

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Asian Journal of Andrology 2024年第2期26卷 212-219页

作者： Gao-Qing Qian Xiao-Chen Wang Xi Zhang Bin Shen Qiang Liu State Key laboratory of Reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjing 211166China Shanghai Key laboratory of Reproductive Medicine Department of HistoembryologyGenetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China State Key laboratory of Molecular Biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Male germ cells employ specific metabolic pathways throughout their developmental *** a previous study,we discovered heightened expression of pyruvate kinase M(PKM),a pivotal glycolytic enzyme,in spermatogonia and *** gain deeper insights into PKM's roles in spermatogenesis,sperm function,and male fertility,we engineered a conditional-knockout mouse model(Pkm-vkO mice)to selectively disrupt the Pkm gene within germ *** maintaining regular testicular histology and sperm morphology,the male Pkm-vko mice were infertility,characterized by significant impairments in sperm motility and adenosine triphosphate(ATP)*** addition,Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation,as well as compromised performance in in vitro fertilization *** conclude,PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells;however,it emerges as a critical factor influencing sperm motility and overall male fertility.

关键词： glycolysis male fertility pyruvate kinase M sperm motility spermatogenesis

Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes

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Science China(Life Sciences) 2024年第8期67卷 1697-1714页

作者： Huan Wu Yanman Zhang Yuqian Li Shuya Sun Jintao Zhang Qingsong Xie Yue Dong Shushu Zhou Xuan Sha Kuokuo Li Jinyi Chen Xin Zhang Yang Gao Qunshan Shen Guanxiong Wang Xiaomin Zha Zongliu Duan Dongdong Tang Chuan Xu Hao Geng Mingrong Lv Yuping Xu Ping Zhou Zhaolian Wei Rong Hua Yunxia Cao Mingxi Liu Xiaojin He Reproductive Medicine Center Department of Obstetrics and GynecologyThe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China State Key laboratory of Reproductive Medicine and Offspring Health Department of Histology and EmbryologySchool of Basic Medical SciencesNanjing Medical UniversityNanjing 210029China State Key laboratory of Reproductive Medicine and Offspring Health The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou School of Clinical MedicineNanjing Medical UniversityNanjing 211166China Reproductive Medicine Center Department of Obstetrics and GynecologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China State Key laboratory of Reproductive Medicine and Offspring Health Clinical Center of Reproductive MedicineThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China NHC Key laboratory of Study on Abnormal Gametes and Reproductive Tract(Anhui Medical University) Hefei 230032China Key laboratory of Population Health Across Life Cycle(Anhui Medical University) Ministry of Education of the People’s Republic of ChinaHefei 230032China Anhui Province Key laboratory of Reproductive Health and genetics Hefei 230032China Biopreservation and Artificial Organs Anhui Provincial Engineering Research CenterAnhui Medical UniversityHefei 230032China

The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across *** shuttles,particularly adenylate kinase(AK)and creatine kinase(CK),are pivotal in the efficient transfer of intracellular ATP,showing distinct tissue-and ***,the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups,of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across *** AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male *** mouse models showed that AK8 and AK9 were central to promoting sperm *** combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke(RS)of the *** of various human and mouse sperm samples with substructural damage,including the presence of multiple RS subunits,showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar *** an ATP probe together with metabolomic analysis,it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme,and were concentrated at sites associated with energy consumption in the *** findings indicate a novel function for RS beyond its structural role,namely,the regulation of ATP *** conclusion,the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.

关键词： adenylate kinase Subgroup III AKs AK8 AK9 male infertility ATP transfer radial spoke

Biomolecular condensates and disease pathogenesis

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Science China(Life Sciences) 2024年第9期67卷 1792-1832页

作者： Ke Ruan Ge Bai Yanshan Fang Dan Li Tingting Li Xingguo Liu Boxun Lu Qing Lu Zhou Songyang Shuguo Sun Zheng Wang Xin Zhang Wen Zhou Hong Zhang The First Affiliated Hospital&School of Life Sciences Ministry of Education Key Laboratory for Membrane-less Organelles&Cellular DynamicsHefei National Research Center for Interdisciplinary Sciences at the MicroscaleCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Nanhu Brain-computer Interface Institute Hangzhou 311100China Department of Neurology of Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of MedicineHangzhou 310058China Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China University of Chinese Academy of Sciences Beijing 100049China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China Department of Biomedical Informatics School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China CAS Key laboratory of Regenerative Biology Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 510000China Neurology Department at Huashan Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceSchool of Life SciencesFudan UniversityShanghai 200433 China Key laboratory for the genetics of Developmental and Neuropsychiatric Disorders Ministry of EducationBio-X InstitutesShanghai Jiao Tong UniversityShanghai 200030China State Key laboratory of Biocontrol MOE Key Laboratory of Gene Function and Regulation and Guangzhou Key Laboratory of Healthy Aging ResearchSchool of Life SciencesSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510275China Department of Human Anatomy Hist

Biomolecular condensates or membraneless organelles(MLOs)formed by liquid-liquid phase separation(LLPS)divide intracellular spaces into discrete compartments for specific *** of LLPS or aberrant phase transition that disturbs the formation or material states of MLOs is closely correlated with neurodegeneration,tumorigenesis,and many other pathological ***,we summarize the recent progress in development of methods to monitor phase separation and we discuss the biogenesis and function of MLOs formed through phase *** then present emerging proof-of-concept examples regarding the disruption of phase separation homeostasis in a diverse array of clinical conditions including neurodegenerative disorders,hearing loss,cancers,and immunological ***,we describe the emerging discovery of chemical modulators of phase separation.

关键词： liquid-liquid phase separation biomolecular condensate membraneless organelle

Oxidative Stress, Biochemical and Histopathological Alterations in the Liver and Kidney of Female Rats Exposed to Low Doses of Deltamethrin (DM):A Molecular Assessment

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Biomedical and Environmental Sciences 2012年第6期25卷 672-683页

作者： CHARGUI Issam GRISSA Intissar BENSASSI Fatma HRIRA Mohamed Yahia HAOUEM Samir HAOUAS Zohra BENCHEIKH Hassen laboratory of histology-cytology and genetics (02/UR/08-03) Faculty of Medicine 5019 Monastir Tunisia laboratory of Research on Biologically Compatible Compounds Faculty of Dentistry Street Avicenne 5019 Monastir Tunisia laboratory of Plant Protection The National Institute for Agricultural Research INRA Tunisia Street Hedi Karray 2049 Ariana Tunisia laboratory of Biochemistry (UR 07/06) Faculty of pharmacy 5019 Monastir Tunisia laboratory of Physiology Faculty of Medicine 5019 Monastir Tunisia

Objective To evaluate histopathological alterations of the liver and kidney of female rats exposed to low doses of DM and its potential genotoxic activity. Methods Female Wistar rats were randomly assigned to control （3 groups, 6 rats in each） and treatment groups （3 groups, 6 rats in each）. They were subjected to subcutaneous injections of DM （at doses of 0.003, 0.03, and 0.3 mg/kg bw/d） after 30, 45, and 60 d, respectively. Results Significant alterations were recorded in liver parenchyma induced by hepatic vacuolization, fragmented chromatin in nuclei, dilatation of sinusoids and congestions. Lesions within proximal and distal tubules were observed in the kidneys. Tissue congestions and severe alterations within glomeruli were visible. DM as a pyrethroid insecticide induced significant increase （P〈_O.05） of plasma MDA concentrations after 45 d. A significant increase （P_〈0.05） in plasma ALT （after 45 and 60 d） and AST （after 60 d） concentrations was recorded as compared to controls. During the whole experimental period the toxic agent provoked significant DNA damages （P〈0.05）, especially in the dominance of classes 3 and 4 of obtained comet. Conclusion DM even at a very low dose displays harmful effects by disrupting hepatic and renal function and causing DNA damages in puberscent female rats. Low doses of DM are hepatotoxic and nephrotoxic.

关键词： Deltamethrin Rats Liver Kidney Histopathology Comet assay DNA damage.

Roles of mitochondrial unfolded protein response in mammalian stem cells

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World Journal of Stem Cells 2021年第7期13卷 737-752页

作者： Li-Fang Gu Jia-Qi Chen Qing-Yin Lin Yan-Zhou Yang Key laboratory of Fertility Preservation and Maintenance Ministry of EducationKey Laboratory of Reproduction and Genetics in NingxiaDepartment of Histology and EmbryologySchool of Basic MedicineNingxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina Key laboratory of Fertility Preservation and Maintenance Ministry of EducationKey Laboratory of Reproduction and Genetics in NingxiaDepartment of Histology and EmbryologySchool of Basic MedicineNingxia Medical UniversityYinchuan 750001Ningxia Hui Autonomous RegionChina

The mitochondrial unfolded protein response(UPRmt)is an evolutionarily conserved adaptive mechanism for improving cell survival under mitochondrial *** physiological and pathological conditions,the UPRmt is the key to maintaining intracellular homeostasis and *** roles of the UPRmt have been demonstrated in a variety of cell types and in cell development,metabolism,and immune *** dysfunction leads to a variety of pathologies,including cancer,inflammation,neurodegenerative disease,metabolic disease,and immune *** cells have a special ability to selfrenew and differentiate into a variety of somatic cells and have been shown to exist in a variety of *** cells are involved in development,tissue renewal,and some disease *** the roles and regulatory mechanisms of the UPRmt in somatic cells have been widely reported,the roles of the UPRmt in stem cells are not fully *** roles and functions of the UPRmt depend on stem cell ***,this paper summarizes the potential significance of the UPRmt in embryonic stem cells,tissue stem cells,tumor stem cells,and induced pluripotent stem *** purpose of this review is to provide new insights into stem cell differentiation and tumor pathogenesis.

关键词： Mitochondrial unfolded protein response Mammals Stem cells Cancer

Increased MAD2L2 expression predicts poor clinical outcome in Colon Adenocarcinoma

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BIOCELL 2023年第3期47卷 607-618页

作者： HAOTONG SUN HEYING WANG XIN LI YANJIE HAO JUN LING HUAN WANG FEIMIAO WANG FANG XU School of Basic Medicine Medical Genetics and Cell BiologyNingxia Medical UniversityYinchuan750004China Key laboratory of Reproduction and genetics Ningxia Medical UniversityYinchuan750004China Department of Human Anatomy and histology Embryology Ningxia Medical UniversityYinchuan750004China

Background:Colon adenocarcinoma(COAD)is the second leading cause of cancer death worldwide thus,identification of COAD biomarkers is *** Arrest Deficient 2 Like 2(MAD2L2)is a key factor in mammalian DNA damage repair and is highly expressed in many malignant *** is a comprehensive study of MAD2L2 expression,its diagnostic value,prognostic analysis,potential biological function,and impact on the immune system of patients with ***:Gene expression,clinical relevance,prognostic analysis,diagnostic value,GO/KEGG cluster analysis,data obtained from TCGA,and bioinformatics statistical analysis were performed using the R *** responses to MAD2L2 expression in COAD were analyzed using *** expression of MAD2L2 in HCT116 cells induced by the inflammatory factor TNF-αwas detected using Western ***:Our results underscore the clinical diagnostic value and potential biological significance of MAD2L2 in patients with COAD.A high level of MAD2L2 expression has been found in COAD and correlated with tumor status and colon *** curve analysis showed that MAD2L2 expression has high diagnostic value in *** of immune infiltration results showed that MAD2L2 expression was positively correlated with neutrophil *** western blot results demonstrated that MAD2L2 was dose-dependently present with TNF-α.GO/KEGG revealed that MAD2L2 overexpressed and coexpressed genes were mostly involved in biological functions,including hypoxia response,response to reduced oxygen levels,mitochondrial translation elongation,and other ***:MAD2L2 as a new COAD biomarker contributes to our understanding of how alterations in gene expression and the immunological environment contribute to the development of colon *** further investigation,MAD2L2 may prove to be a viable target factor for clinical diagnosis and therapy of COAD.

关键词： MAD2L2 COAD Poor prognosis Immune infiltration TCGA

Vitamin B12-induced spermatogenesis recovery in cimetidine-treated rats： effect on the spermatogonia number and sperm concentration

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Asian Journal of Andrology 2017年第5期19卷 567-572页

作者： Flavia L Beltrame Estela Sasso-Cerri Department of Morphology and genetics Federal University of Sao Paulo (UNIFESP/EPM) Sao Paulo Brazil Department of Morphology Laboratory f Histology and Embryology Dental School - Sao Paulo State University (UNESP/FOAr) Araraquara Sao Paulo Brazil

The H2-receptor antagonist cimetidine is an antiulcer drug also used for the treatment of cancer due to its antiangiogenic effect. However, this drug has caused structural changes in the seminiferous tubules. Vitamin B12 has been used as a therapeutic agent for the treatment of male infertility. The supplementation of rats with vitamin B12 during cimetidine treatment has recovered the damaged seminiferous tubules, but how this vitamin restores the seminiferous epithelium has not been clarified. In this study, we evaluated whether vitamin B12 improves the number of spermatogonia, spermatocytes, and sperm concentration in cimetidine-treated rats. Adult male rats were treated for 50 days as follows： cimetidine group received 100 mg kg^-1 b.w. of cimetidine, cimetidine-B12 group received cimetidine and 3 μg of vitamin B12-hydroxocobalamin, B12 group received only 3 μg of vitamin, and control group received saline. Sperm concentration was calculated and historesin-embedded testes sections were used for the quantitative analyses of spermatogonia （A; In/B） and spermatocytes. TUNEL method and PCNA immunofluorescence were performed. Cimetidine caused a significant reduction in sperm concentration. TUNEL-positive spermatogonia and spermatocytes were correlated to a significant reduction in the number of these cells. In cimetidine-B12 group, sperm concentration was higher than cimetidine group and a significant increase in the number of spermatogonia （stages Ⅱ-Ⅵ） was correlated to a high incidence of PCNA-immunolabeled spermatogonia and spermatocytes. The results show that the supplementation of rats with vitamin B12 during cimetidine treatment increases sperm concentration and exerts a potential effect in the recovery of spermatogonia and spermatocytes.

关键词： cimetidine fertility spermatogenesis testis vitamin B12

Induced pluripotent stem cells for modeling and cell therapy of Parkinson＇s disease

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Neural Regeneration Research 2016年第5期11卷 727-728页

作者： Mária Csobonyeiová Lubos Danisovic Stefan Polák Institute of histology and Embryology Faculty of Medicine Comenius University in Bratislava Bratislava Slovakia Institute of Medical Biology Genetics and Clinical Genetics Faculty of Medicine Comenius University in Bratislava Bratislava Slovakia

Neurodegenerative disorders include a variety of hereditary or sporadic diseases involving the chronic,progressive loss on neural ***＇s disease（PD）is the second most common neurodegenerative disease,affecting more than 6 million people worldwide（Wan et al.,2015）.Degeneration of nigrostriatal dopamine（DA）neurons is the main pathology in PD.

关键词： INDUCTION IPSCS