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Aging hallmarks of the primate ovary revealed by spatiotemporal transcriptomics

Protein & Cell 2024年第5期15卷 364-384页

作者： Huifen Lu Ying Jing Chen Zhang Shuai Ma Weiqi Zhang Daoyuan Huang Bin Zhang Yuesheng Zuo Yingying Qin Guang-Hui Liu Yang Yu Jing Qu Si Wang Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem cell and Regeneration CASBeijing 100101China China National Center for Bioinformation Beijing 100101China The Fifth People’s Hospital of Chongqing Chongqing 400062China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking UniversityThird HospitalBeijing 100191China Clinical Stem Cell Research Center Peking UniversityThird HospitalBeijing 100191China Center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250012China Key Laboratory of Reproductive Endocrinology of Ministry of Education National Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthJinan 250012China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Biomarker Consortium Beijing 100101China

The ovary is indispensable for female reproduction,and its age-dependent functional decline is the primary cause of infertility.However,the molecular basis of ovarian aging in higher vertebrates remains poorly understood.Herein,we apply spatiotemporal transcriptomics to benchmark architecture organization as well as cellular and molecular determinants in young primate ovaries and compare these to aged primate ovaries.From a global view,somatic cells within the non-follicle region undergo more pronounced transcriptional fluctuation relative to those in the follicle region,likely constituting a hostile microenvironment that facilitates ovarian aging.Further,we uncovered that inflammation,the senescent-associated secretory phenotype,senescence,and fibrosis are the likely primary contributors to ovarian aging(PCOA).Of note,we identified spatial co-localization between a PCOA-featured spot and an unappreciated MT2(Metallothionein 2)highly expressing spot(MT2^(high))characterized by high levels of inflammation,potentially serving as an aging hotspot in the primate ovary.Moreover,with advanced age,a subpopulation of MT2^(high)accumulates,likely disseminating and amplifying the senescent signal outward.Our study establishes the first primate spatiotemporal transcriptomic atlas,advancing our understanding of mechanistic determinants underpinning primate ovarian aging and unraveling potential biomarkers and therapeutic targets for aging and age-associated human ovarian disorders.

关键词： spatial transcriptome primate ovary aging senescence inflammation

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Molybdenum and cadmium co-induce necroptosis through Th1/Th2 imbalance-mediated endoplasmic reticulum stress in duck ovaries

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Journal of Environmental Sciences 2024年第8期142卷 92-102页

作者： Ting Cui Xueyan Dai Huiling Guo Dianyun Wang Bingyan Huang Wenjing Pu Xuesheng Chu Caiying Zhang Jiangxi Provincial Key Laboratory for Animal Health Institute of Animal Population HealthCollege of Animal Science and TechnologyJiangxi Agricultural UniversityNanchang 330045China

Cadmium(Cd)and excess molybdenum(Mo)pose serious threats to animal health.Our previous study has determined that Cd and/or Mo exposure can cause ovarian damage of ducks,while the specific mechanism is still obscure.To further investigate the toxic mechanism of Cd and Mo co-exposure in the ovary,forty 8-day-old female ducks were randomly allocated into four groups for 16 weeks,and the doses of Cd and Mo in basic diet per kg were as follows:control group,Mo group(100 mg Mo),Cd group(4 mg Cd),and Mo+Cd group(100 mg Mo+4 mg Cd).Cadmium sulfate 8/3-hydrate(CdSO_(4)·8/3H_(2)O)and hexaammonium molybdate((NH_(4))_(6)Mo_(7)O_(24)·4H_(2)O)were the origins of Cd and Mo,respectively.At the 16th week of the experiment,all ovary tissues were collected for the detection of related indexes.The data indicated that Mo and/or Cd induced trace element disorders and Th1/Th2 balance to divert toward Th1 in the ovary,which activated endoplasmic reticulum(ER)stress and then provoked necroptosis through triggering RIPK1/RIPK3/MLKL signaling pathway,and eventually caused ovarian pathological injuries and necroptosis characteristics.The alterations of above indicators were most apparent in the joint group.Above all,this research illustrates that Mo and/or Cd exposure can initiate necroptosis through Th1/Th2 imbalance-modulated ER stress in duck ovaries,and Mo and Cd combined exposure aggravates ovarian injuries.This research explores the molecular mechanism of necroptosis caused by Mo and/or Cd,which reveals that ER stress attenuation may be a therapeutic target to alleviate necroptosis.

关键词： Molybdenum Cadmium Th1/Th2 imbalance Endoplasmic reticulum stress Necroptosis ovary

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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 erasers.The fat-mass and obesity-associated protein(FTO)catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes.Our 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 expression.Application 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 splicing.Overexpression 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 follicles.Conversely,overexpression of Fto lacking a nuclear localization signal(NLS)did not significantly alter m6A levels or primordial follicle assembly.These 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 assembly.These 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

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Hexamerin and allergen are required for female reproduction in the American cockroach,Periplaneta americana

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Insect Science 2024年第1期31卷 186-200页

作者： Shiming Zhu Xiaoyi Chen Sishi Xia Qin Li Ziqi Ye Shaoting Zhao Kexin Liu Fangfang Liu Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology Institute of Insect Science and TechnologyInstitute of Insect Science and Technology&School of Life SciencesSouth China Normal UniversityGuangzhouChina Guangmeiyuan R&D Center Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied TechnologySouth China Normal UniversityMeizhouGuangdong ProvinceChina Guangdong Laboratory for Lingnan Modern Agriculture South China Agricultural UniversityGuangzhouChina

Reproduction is of great importance for the continuation of the species.In insects,the fat body is the major tissue for nutrient storage and involved in vitellogenesis,which is essential for female reproduction.Here,2 proteins,hexamerin and allergen,were separated from the fat bodies of adult female American cockroaches(Periplaneta americana)and identified as storage proteins,encoding for 733 amino acids with molecular weight of 87.88 kDa and 686 amino acids with molecular weight of 82.18 kDa,respectively.The encoding genes of these 2 storage proteins are mainly expressed in the fat body.RNA interference-mediated knockdown of Hexamerin and Allergen in the early stage of the first reproductive cycle in females suppressed vitellogenesis and ovarian maturation,indicating that these storage proteins are involved in controlling reproduction.Importantly,the expression of Hexamerin and Allergen was repressed by knockdown of the juvenile hormone(JH)receptor gene Met and the primary response gene Kr-h1,and was induced by methoprene,a JH analog,in both in vivo and in vitro experiments.Altogether,we have determined that hexamerin and allergen are identified as storage proteins and play an important role in promoting female reproduction in the American cockroach.The expression of their encoding genes is induced by JH signaling.Our data reveal a novel mechanism by which hexamerin and allergen are necessary for JH-stimulated female reproduction.

关键词： fat body juvenile hormone ovary reproduction storage protein vitellogenesis

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Clinical analysis of 12 cases of ovarian neuroendocrine carcinoma

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World Journal of Clinical Cases 2024年第6期12卷 1111-1119页

作者： Xiao-Yu Xing Wei Zhang Li-Ya Liu Li-Ping Han Department of Gynecology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000Henan ProvinceChina

BACKGROUND Neuroendocrine neoplasms of the female genital tract are rare.AIM To enhance our clinical understanding of neuroendocrine carcinoma(NEC)of the ovary.METHODS A retrospective review was conducted on 12 patients diagnosed with NEC of the ovary,analyzing clinicopathological characteristics,treatment modalities,and survival status.RESULTS The median age at diagnosis was 34.5 years(range:20 to 62 years).Among the 12 cases,9 were small cell carcinoma of the ovary and 3 were large cell NEC.Five cases were stage I tumors,one case was stage IV,and six cases were stage III.Eleven patients underwent surgery as part of their treatment.All patients received adjuvant chemotherapy.Among the 12 patients,one patient received radiotherapy,and one patient with a BRCA2 mutation was administered PARP inhibitor maintenance after chemotherapy.The median progression-free survival was 13 months,and the median overall survival was 19.5 months.Four cases remained disease-free,while eight cases experienced tumor recurrence,including three cases that resulted in death due to disease recurrence.CONCLUSION NEC of the ovary is a rare condition that is more common in women of childbearing age and is associated with aggressive behavior and poor clinical outcomes.Surgical resection remains the mainstay of treatment,with some patients benefiting from adjuvant chemoradiation therapy.

关键词： Neuroendocrine carcinoma ovary Pathology Treatment

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Characterization and expression analysis of gonad specific igf3 in the medaka ovary

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Aquaculture and Fisheries 2022年第3期7卷 259-268页

作者： Jiale Xie Ying Zhong Yuli Zhao Wenjie Xie Jing Guo Lang Gui Mingyou Li International Research Center for Marine Biosciences Ministry of Science and TechnologyShanghai Ocean UniversityChina Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources Ministry of EducationShanghai Ocean UniversityShanghai201306China

The gonad specific expression of insulin-like growth factor 3(igf3)has suggested an important role of igf3 in fish reproduction.In this study,medaka igf3 was isolated and its expression patterns were compared with igf1,and germ cell gene vasa in adult medaka ovary.Molecular cloning and sequencing showed that the open reading frame(ORF)of medaka igf3 was comprised of 501 nucleotides and encoded 166 amino acid residues.Reverse transcription polymerase chain reaction(RT-PCR)analysis showed that igf3 RNA was specifically expressed in developing embryos and adult gonads of both sexes.Real time quantitative PCR(q-PCR)indicated that igf3 expression was gradually increased during oogenesis,and reached its highest level at stage V.Using Chromogenic and fluorescent in situ hybridization,igf3 was shown to be present in the germ cells of oogonia and in oocytes at stages I-III,as well as abundant in granulosa cells and theca cells of oocytes at stages IV-V.In addition,igf3 and igf1 were expressed mutually in the outer theca cells of stage V oocytes in ovary.Collectively,we demonstrated that gonad specific igf3 could mark medaka ovarian somatic cells and germ cells.These findings highlight the importance of igf3 during ovarian development.

关键词： igf3 igf1 Medaka ovary

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Primary sarcoma of the ovary： clinicopathological characteristics, prognostic factors and evaluation of therapy

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Chinese Medical Journal 2011年第9期124卷 1316-1321页

作者： DAI Yi SHEN Keng LANG Jing-he HUANG Hui-fang PAN Ling-ya WU Ming YANG Jia-xin ZHONG Ding-rong Department of Obstetrics and Gynecology Peking Union Medical College HospitalPeking Union Medical College & Chinese Academy of Medical Sciences Beijing 100730 China Department of Pathology Peking Union Medical College HospitalPeking Union Medical College & Chinese Academy of Medical Sciences Beijing 100730 China

Background The primary ovarian sarcoma is a very rare malignancy. The objective of this study was to further investigate the clinicopathologic features and outcome in patients with primary sarcoma of the ovary.Methods Between 1988 and 2007, 24 patients with primary ovarian sarcoma who underwent treatment at Peking Union Medical Hospital were reviewed retrospectively. Response to treatment, progression and overall survival were analyzed.Results Patients with ovarian sarcoma had a mean age of （54.3±10.3） years, and 16 of them were postmenopausal.The most common symptom was abdominal pain, present in 14 patients. Of the 24 patients, 16 patients were pathologically diagnosed as carcinosarcoma （known as malignant mixed mesodermal tumor （MMMT））, 2 as ovarian leiomyosarcoma （LS） and 6 patients as ovarian endometrial stromal sarcoma （ESS）. The patients in optimal debulking group had a median survival period of 28 months and 1-year survival rate of 71%. The patients in suboptimal debulking group had a significantly lower median survival of 6 months （P=-0.02） and 1-year survival rate of 29%. Among the patients,23 patients received chemotherapy and most of regimens were based on platinum, 3 patients received chemoradiation.The mean number of courses of combined chemotherapy was 6.6±5.0, and the response was unsatisfactory. The median survival for the entire group was 18.7 months. The one-year survival rate was 58%, and two-year survival rate only 29%.Conclusions Ovarian primary sarcoma has a poor overall prognosis. Optimal debulking surgery appears to be of prognostic significance. There is a clear need for further study to explore the role and the regimen of platinum-based chemotherapy in primary ovarian sarcoma.

关键词： ovary sarcoma chemotherapy

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Identification of Sheep ovary Genes Potentially Associated with Off-season Reproduction

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Journal of Genetics and Genomics 2012年第4期39卷 181-190页

作者： Lei Chen Ka Liu Zongsheng Zhao Hugh T.Blair Peng Zhang Daquan Li Runlin Z.Ma College of Animal Science and Technology Shihezi UniversityXinjiang 832000China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Institute of Veterinary Animal and Biomedical Sciences Massey UniversityNew Zealand IGDB-Massey Joint Research Center for Sheep Breeding and Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Off-season reproduction is a favorable economic trait for sheep industry. Hu sheep, an indigenous Chinese sheep breed, demonstrates a higher productivity of lambs and displays year-around oestrous behavior under proper nutrition and environment. The genetic basis behind these traits, however, is not well understood. In order to identify genes associated with the off-season reproduction, we constructed a suppression subtractive hybridization （SSH） cDNA library using pooled ovary mRNAs of 6 oestrous Hu females as a tester and the pooled ovary mRNAs of 6 non-oestrous Chinese Merino females as a driver. A total of 382 resulting positive clones were obtained after the SSH. We identified 114 differentially up-regulated genes in oestrous Hu sheep by using subsequent screening and DNA sequencing, of which 8 were previously known, 93 were reported for the first time in sheep, and 13 were novel with no significant homology to any sequence in the DNA databases. Functions of the genes identified are related to cell division, signal transduction, structure, metabolism, or cell defense. To validate the results of SSH, 6 genes （Ntrk2, Ppap2b, Htral, Nidl, Serpine2 and Foxola） were selected for conformational analysis using quantitative real-time PCR （qRT-PCR）, and two of them （Htral and Foxola） were verified by Northern blot. All of the 6 genes were differentially up-regulated in the ovary of oestrous Hu. It is obvious that off-season reproduction is a complex trait involving multiple genes in multiple organs. This study helps to provide a foundation for the final identification of functional genes involved in the sheep ovary.

关键词： Hu sheep Suppression subtractive hybridization Oestrous ovary cDNA library

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Community structure, dispersal ability and functional profiling of microbiome existing in fat body and ovary of the brown planthopper, Nilaparvata lugens

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Insect Science 2019年第4期26卷 683-694页

作者： Jian-Hua Zhang Na Yu Xi-Xia Xu Ze-Wen Liu Key laboratory of Integrated Management of Crop Diseases and Pests (Ministry of Education) College of Plant Protection Nanjing Agricultural University Nanjing China

The endosymbionts play vital roles in growth, development and reproduction in insects. Yeast-like endosymbionts (YLSs) have been well studied in Nilaparvata lugens (N. lugens), but little is known about the tissue-specific bacterial microbiomes, especially on the microbial intersection among internal tissues. Here, the correlation of microbial composition, structure, dispersal ability and functional profiling were illuminated in two tissues, the fat body and ovary in N. lugens. A total of 11 phyla and 105 genera were captured from all samples;Firmicutes and Proteobacteria were the most predominant and accounted for more than 99% in all samples. However, the relative abundance ofFirmicutes and Proteobacteria was significantly different in ovary and fat body through Fisher's Least Significant Difference test. Microbial diversity but not the richness index in the two tissues exhibited significant difference. Furthermore, the microbial community structure of the ovary and fat body were primarily determined by tissue quality. Firmicutes showed strong dispersal ability between ovary and fat body based on the quantitative null model assessing, indicating the frequent interaction of these microbiomes in the two tissues. In addition, the Kyoto Encyclopedia of Genes and Genomes pathways of microbial participation were delineated. The ten most abundant pathways counted for over 46% of the annotation and were shared between the two tissues, mainly containing Energy Metabolism and Amino Acid Metabolism/Biosynthesis. The results will provide insights into the correlation of microbial community structure between ovary and fat body of N. lugens.

关键词： dispersal ability fat body functional profiling microbial structure Nilaparvata lugens ovary

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Flexible GnRH Antagonist Protocol versus Progestin-primed Ovarian Stimulation (PPOS) Protocol in Patients with Polycystic ovary Syndrome: Comparison of Clinical Outcomes and Ovarian Response

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Current Medical Science 2019年第3期39卷 431-436页

作者： Zhuo-ni XIAO Jia-li PENG Jing YANG Wang-ming XU Center for Reproductive Medicine Renmin Hospital of Wuhan University Wuhan 430060China

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.

关键词： polycystic ovary syndrome ovarian hyperstimulation syndrome progestin-primed ovarian stimulation GnRH antagonist protocol controlled ovarian hyperstimulation

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