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Dissecting the cell microenvironment of ovarian endometrioma through single-cell RNA sequencing

Science China Life Sciences 2025年第1期68卷 116-129页

作者： Jiangpeng Wu Siyu Xia Wenting Ye Yan Sun Jing Cai Fubing Yu Haiping Wen Xiuwei Yi Taikang Li Mingwei Chen Jiayun Chen Ge Song Chuanbin Yang Yali Song Jigang Wang Department of reproductive medicine Dongguan Maternal and Child Health Care Hospital Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalSouthern University of Science and Technology State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences reproductive medicine Center Foshan Women and Children Hospital State Key Laboratory of Antiviral Drugs School of PharmacyHenan University

Ovarian endometrioma（OE）, also known as “chocolate cysts,” is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+and KLF2+epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies.

关键词： ovary high-throughput sequencing transcriptomics gene expression analysis ligand-receptor analysis

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Insufficient MIRO1 contributes to declined oocyte quality during reproductive aging

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Science China Life Sciences 2025年

作者： Zhen-Nan Pan Hao-Lin Zhang Kun-Huan Zhang Jia-Qian Ju Jing-Cai Liu Shao-Chen Sun College of Animal Science and Technology Nanjing Agricultural University reproductive medicine Centre The Affiliated Yantai Yuhuangding Hospital of Qingdao University

Mitochondrial Rho-GTPase 1 (MIRO1) is an outer mitochondrial membrane protein which regulates mitochondrial transport and mitophagy in mitosis. In present study, we reported the crucial roles of MIRO1 in mammalian oocyte meiosis and its potential relationship with aging. We found that MIRO1 expressed in mouse and porcine oocytes, and its expression decreased in aged mice. MIRO1 deficiency caused the failure of meiotic resumption and polar body extrusion in both mouse and porcine oocytes, which could be rescued by exogenous MIRO1supplementation. Mass spectrometry data indicated that MIRO1 associated with several cytoskeleton and cell cycle-related proteins, and MIRO1 regulated motor protein Dynein for microtubule-organizing centers (MTOCs) dynamics at germinal vesicle (GV) stage, which determined meiotic resumption. Furthermore, we found that MIRO1 regulated Aurora A and kinesin family member 11 (KIF11) for meiotic spindle assembly in oocytes. Besides, MIRO1 associated with several mitochondria-related proteins dynamic-related protein 1 (DRP1),Parkin and lysosomal-associated membrane protein 2 (LAMP2) for mitochondrial dynamics and mitophagy during oocyte meiosis. Taken together, our results suggested that MIRO1 played pivotal roles in meiotic resumption, spindle assembly and mitochondrial function in mouse and porcine oocytes, and its insufficiency might contribute to the oocyte maturation defects during aging.

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Autophagy-targeting modulation to promote peripheral nerve regeneration

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Neural Regeneration Research 2025年第7期20卷 1864-1882页

作者： Yan Chen Hongxia Deng Nannan Zhang Department of Obstetrics and gynecology West China Second HospitalSichuan UniversityChengduSichuan ProvinceChina Key Laboratory of Birth Defects and Women and Children’s Diseases Ministry of EducationSichuan UniversityChengduSichuan ProvinceChina Laboratory of reproductive Endocrinology and reproductive Regulation Sichuan UniversityChengduSichuan ProvinceChina National Center for Birth Defect Monitoring West China Second University HospitalSichuan UniversityChengduSichuan ProvinceChina

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular *** studies have focused on factors that stimulate axonal outgrowth and myelin ***,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic ***,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve *** current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and *** actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve *** review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this *** hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

关键词： autophagy autophagy related genes Charcot–Marie–Tooth diseases diabetic peripheral neuropathy metformin myelination peripheral nerve injury Schwann cells sciatic nerve Wallerian degeneration

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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu Michael Chopp Michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of Pathology Henry Ford HospitalDetroitMIUSA Division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

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Intrauterine insemination with donor sperm:only the number of motile spermatozoa inseminated influences both pregnancy and live-birth rates

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Asian Journal of Andrology 2022年第3期24卷 287-293页

作者： Marie Cardey-Lefort Berengere Ducrocq Audrey Uk Helen Behal Anne-Laure Barbotin Geoffroy Robin reproductive Biology Institute Lille University HospitalLille F-59037France Lille University Lille University HospitalULR 2694-METRICSLille F-59000France endocrine gynecology and reproductive medicine unit Lille University HospitalLille F-59037France

Intrauterine insemination with donor sperm(IUI-D)is an assisted reproductive technology(ART)offered to couples with definitive male infertility or risk of genetic disease ***,we sought to evaluate our practice in IUI-D and identify factors that influenced the success *** performed a retrospective,single-center study of all IUI-D procedures performed at Lille University Medical Center(Lille,France)between January 1,2007,and December 31,*** and multivariate analyses with a mixed logistic model were used to identify factors associated with clinical pregnancies and live *** included 322 couples and 1179 IUI-D *** clinical pregnancy rate was 23.5%,and the live birth rate was 18.9%per *** a multivariate analysis,the women’s age was negatively associated with the live birth *** number of motile spermatozoa inseminated was the only factor associated with both clinical pregnancies and live births,with a chosen threshold of 0.75 *** clinical pregnancy and live birth rates were,respectively,17.3%and 13.0%below the number of motile spermatozoa inseminated threshold and 25.9%and 21.0%at or above the threshold(all P=0.005).The number of motile spermatozoa inseminated was the only factor that significantly influenced both pregnancies and live-birth rates after ***,below a threshold of 0.75 million motile spermatozoa inseminated,those rates were significantly *** of this number of motile spermatozoa inseminated threshold may help centers to allocate donations more effectively while maintaining reasonable waiting times for patients.

关键词： intrauterine insemination male infertility number of motile spermatozoa inseminated sperm donor

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Pan-TRK positive uterine sarcoma in immunohistochemistry without neurotrophic tyrosine receptor kinase gene fusions:A case report

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World Journal of Clinical Cases 2025年第2期13卷 39-49页

作者： Seungmee Lee Yu-Ra Jeon Changmin Shin Sun-Young Kwon Sojin Shin Department of Obstetrics and gynecology Keimyung University School of MedicineDaegu 42601South Korea Department of Pathology and Institute for Cancer Research Keimyung University School of MedicineDaegu 42601South Korea

BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic *** on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent ***-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion *** SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic *** examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK ***,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage *** The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive *** such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.

关键词： Uterine sarcoma Cervical sarcoma Neurotrophic tyrosine receptor kinase gene fusion Next generation sequencing Case report

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CD56^brightCD25^＋ NK cells are preferentially recruited to the maternal/fetal interface in early human pregnancy

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Cellular & Molecular Immunology 2015年第1期12卷 77-86页

作者： Yu Tao Yan-Hong Li Hai-Lan Piao Wen-Jie Zhou Di Zhang Qiang Fu Song-Cun Wang Da-Jin Li Mei-Rong Du Laboratory for reproductive Immunology Hospital and Institute of Obstetrics and Gynecology Fudan University Shanghai Medical College Shanghai KeyLaboratory of Female Reproductive Endocrine Related Diseases Shanghai China

Decidual natural killer （dNK） cells are believed to be critical for maintaining maternal/fetal tolerance and regulating placental vascular remodeling based upon their abundance and unique phenotype during early pregnancy. However, the mechanism for how the dNK cells play such important roles in successful pregnancy remains undefined. Here, we identified a subtype of dNK cells characterized as having a CD3-CD56^brightCD25^＋ phenotype. We found that CD56^brightCD25^＋ NK cells preferentially localize to the maternal/fetal interface during early human pregnancy. CD25^＋ dNK cells account for approximately 75% of CD25-expressing decidual immune cells （DICs）. However, less than 5% of CD25-positive peripheral blood mononuclear cells are CD25^＋ NK cells. Furthermore, CD25^＋ and CD25^- dNK cells exhibit distinct phenotypes： CD25^＋ dNK cells display a more activated phenotype and greater cytokine-secreting capacity. Interestingly, coculture of peripheral NK （pNK） cells with primary trophoblasts upregulates the percentage of CD25-expressing pNK cells, resulting in increased expression of activation markers and cytokine production by pNK cells. In addition, we demonstrated that the CXCL12/CXCR4 axis is crucial for the recruitment of CD25^＋ dNK cells and contributes to the accumulation of CD3^-CD56^brightCD25^＋ dNK cells at the maternal/fetal interface. Thus, our data reveal that the crosstalk between trophoblasts and pNK cells leads to the accumulation of CD3^-CD56^brightCD25^＋ dNK cells, which exert a regulating effect at the maternal/fetal interface.

关键词： CXCL12/CXCR4 CD3^-CD56^brightCD25^+ N K cells maternal/fetal interface trophoblasts

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Peri-centrosomal localization of small interfering RNAs in C. elegans

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Science China Life Sciences 2025年

作者： Qile Jin Xuezhu Feng Minjie Hong Ke Wang Xiangyang Chen Jiewei Cheng Yan Kuang Xiaoyue Si Mingjing Xu Xinya Huang Shouhong Guang Chengming Zhu Department of Obstetrics and gynecology The First Affiliated Hospital of USTC The USTC RNA Institute Hefei National Research Center for Physical Sciences at the Microscale School of Life Sciences Division of Life Sciences and Medicine Biomedical Sciences and Health Laboratory of Anhui Province University of Science and Technology of China School of Basic medicine Anhui Medical University

The centrosome is the microtubule-organizing center and a crucial part of cell division. Centrosomal RNAs(cnRNAs) have been reported to enable precise spatiotemporal control of gene expression during cell division in many species. Whether and how cnRNAs exist in C. elegans are unclear. Here, using the nuclear RNAi Argonaute protein NRDE-3 as a reporter, we observed potential peri-centrosome localized small interfering(si)RNAs in C. elegans. NRDE-3 was previously shown to associate with pre-mRNAs and pre-rRNAs via a process involving the presence of complementary siRNAs. We generated a GFP-NRDE-3 knock-in transgene through CRISPR/Cas9 technology and observed that NRDE-3 formed peri-centrosomal foci neighboring the tubulin protein TBB-2, other centriole proteins and pericentriolar material(PCM)components in C. elegans embryos. The peri-centrosomal accumulation of NRDE-3 depends on RNA-dependent RNA polymerase(RdRP)-synthesized 22G siRNAs and the PAZ domain of NRDE-3, which is essential for siRNA binding. Mutation of eri-1, ergo-1, or drh-3 significantly increased the percentage of pericentrosome-enriched NRDE-3. At the metaphase of the cell cycle, NRDE-3 was enriched in both the peri-centrosomal region and the spindle. Moreover, the integrity of centriole proteins and pericentriolar material(PCM) components is also required for the peri-centrosomal accumulation of NRDE-3. Therefore, we concluded that siRNAs could accumulate in the pericentrosomal region in C. elegans and suggested that the peri-centrosomal region may also be a platform for RNAi-mediated gene regulation.

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Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis

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Science China Life Sciences 2025年

作者： Chuan Ye Xuemei Wang Jun Lin Chenyang Wu Yuhua Gao Chenghao Guo Yunxi Liao Ziyan Rao Shaodong Huang Weixuan Chen Ying Huang Jinpeng Sun Dongyu Zhao Changtao Jiang Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third Hospital Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Department of Biomedical Informatics School of Basic Medical SciencesPeking University State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking University State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyPeking University Third Hospital National Clinical Research Center for Obstetrics and gynecology Peking University Third Hospital Department of Endocrinology and Metabolism Peking University Third Hospital Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University Department of Immunology School of Basic Medical SciencesPeking University

Adipogenesis is the healthy expansion of white adipose tissue (WAT),serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the ***,the identification of novel regulatory molecules in adipogenesis,specifically membrane receptors such as G protein-coupled receptors (GPCRs),holds significant clinical *** receptors can serve as viable targets for pharmaceuticals,offering potential for restoring metabolic homeostasis in individuals with *** utilized trajectory inference methods to analyze three distinct single-nucleus sequencing (sNuc-seq) datasets of adipose tissue and systematically identified GPCRs with the potential to regulate *** verification in primary adipose progenitor cells (APCs) of mice,we discovered that ADGRD1 promoted the differentiation of APCs,while GPR39 inhibits this *** the obese mouse model induced by a high-fat diet(HFD),both gain-of-function and loss-of-function studies validated that ADGRD1 promoted adipogenesis,thereby improving metabolic homeostasis,while GPR39 inhibited adipogenesis,leading to metabolic ***,through the analysis of 2,400 ChIP-seq data and 1,204 bulk RNA-seq data,we found that the transcription factors (TFs) MEF2D and TCF12 regulated the expression of ADGRD1and GPR39,*** study revealed the regulatory role of GPCRs in adipogenesis,providing novel targets for clinical intervention of metabolic dysfunction in obese patients.

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Synthesis of 11β-ether-17α-ethinyl-3,17β-estradiols with strong ER antagonist activities

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Chinese Chemical Letters 2014年第4期25卷 567-570页

作者： Jing-Xin Zhang David C.Labaree Richard B.Hochberg Department of Obstetrics Gynecology & Reproductive SciencesYale University School of Medicine

We have previously found that several families of nonpolar short chain 11β-ethers and esters ofestradiol are selective estrogen receptor modulators （SERMs）. Surprisingly, the transformation from potent estrogen to anti-estrogen occurs when the 11β-side chain is increased slightly in length from four to five non-hydrogen atoms. To generate strong antagonists for preclinical development, we have synthesized other similar ER ligands with 11β-ethers and with an additional ethinyl group at the 17β-position in order to slow metabolism of the steroidal moiety. Here we report the synthesis and biological activity of two such compounds （11β-i-PrO-propyl and 11β-t-BuO-propyl ethers） with extremely strong antagonist activities.

关键词： Estrogen receptor SERM Antagonist Estradiol

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