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Ginsenoside Rb1 inhibits oxidative stress-induced ovarian granulosa cell injury through Akt-FoxO1 interaction

Science China(Life Sciences) 2022年第11期65卷 2301-2315页

作者： Ping Zhou Feng Deng Zi Yang Canhui Cao Hongcui Zhao Fenting Liu Ke Zhong Lin Fu Tianliu Peng Di Sun Hui Liu Rong Li Yang Yu Center for Reproductive Medicine Department of Obstetrics and GynecologyPeking University Third HospitalBeijing 100191China Key Laboratory of Assisted Reproduction(Peking University) Ministry of EducationBeijing 100191China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Beijing 100191China National Clinical Research Center for Obstetrics and Gynecology(Peking University Third Hospital) Beijing 100191China Clinical Stem cell Research Center Peking University Third HospitalBeijing 100191China

Ginsenoside Rb1 shows a strong antioxidant effect and has potential activation effects on *** aim of the present study was to investigate the protective effect of Rb1 on age-related ovarian granulosa cell *** granulosa cells(GCs)were obtained from 50 young women(≤30 years)and 50 aged women(≥38 years)at an IVF *** and aged ICR mice were administered with or without Rb1(10 mg kg^(-1),i.p.)for 2 *** protective effects of Rb1 were investigated and the role of Rb1 on the modulation of Akt-FoxO1 interaction was determined with immunofluorescence,Western blotting,immunoprecipitation,si RNA silencing and pharmacological ***1 effectively decreased LDH and MDA,and reversed the apoptotic-related protein levels in h GL cells from old *** results were found in *** addition,the mitochondrial membrane potential was restored and the overaccumulation of ROS was reversed by ***1 preserved peroxide-impaired Akt activation,to some extent,by increasing phosphorylation at ***1 also facilitated p-Akt binding to FoxO1 and promoted the phosphorylation of *** RNA silencing of Akt,Akt inhibitor LY294002,and FoxO1 inhibitor AS1842856 attenuated the effects of *** Rb1 inhibits age-related GCs oxidative damage by activating Akt phosphorylation at Ser473 and by further interaction with FoxO1.

关键词： ginsenoside Rb1 oxidative stress aging granulosa cell Akt FoxO1

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granulosa cell Biomarkers to Predict Oocyte and Embryo Quality in Assisted Reproductive Technology

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Reproductive and Developmental Medicine 2021年第1期5卷 30-37页

作者： Ruo-Han Huang Wen-Hui Zhou Medical Center for Human Reproduction of Beijing Chao-Yang Hospital Beijing 100020China

With the development of human assisted reproductive technology(ART),an objective,accurate,and non-invasive method to assess the quality and viability of oocytes and embryos remains one of the most significant *** cells(GCs)play an essential role in oocyte *** can differentiate into mural GCs(MGCs)and cumulus cells(CCs)under the influence of *** promote the growth and development of follicles by secreting cytokines and steroid ***,CCs can form cumulus-oocyte complexes to communicate with oocytes through gap junctions and promote oocyte growth and *** suitable biomarkers in GCs provides a direction for the non-invasive assessment of oocyte and embryo abilities during ART *** date,only a few studies have investigated potentially effective GC biomarkers during ART processes,such as the apoptosis of GCs,transcriptomic characteristics of GCs,quality and quantity of mitochondria in GCs,and telomere length of such *** are potential reference indices for screening high-quality oocytes and *** studies on MGCs and CCs can provide more effective *** there is scope for optimization and improvement,the results have become increasingly accurate with the constant advances in *** to the heterogeneity of the study population and technical limitations,clinical tests for GCs cannot be performed as part of routine tests,but their prospects are *** article reviews the biomarkers that have been studied in MGCs and CCs.

关键词： Assisted Reproductive Embryo Quality granulosa cell Oocyte Competence

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Transcriptome Dynamics and cell Dialogs Between Oocytes and granulosa cells in Mouse Follicle Development

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 93-106页

作者： Wenju Liu Chuan Chen Yawei Gao Xinyu Cui Yuhan Zhang Liang Gu Yuanlin He Jing Li Shaorong Gao Rui Gao Cizhong Jiang Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem cell Research Tongji UniversityShanghai 200092China Department of Epidemiology and Biostatistics Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineSchool of Public HealthNanjing Medical UniversityNanjing 210029China

The development and maturation of follicles is a sophisticated and multistage *** dynamic gene expression of oocytes and their surrounding somatic cells and the dialogs between these cells are critical to this *** this study,we accurately classified the oocyte and follicle development into nine stages and profiled the gene expression of mouse oocytes and their surrounding granulosa cells and cumulus *** clustering of the transcriptomes showed the trajectories of two distinct development courses of oocytes and their surrounding somatic *** expression changes precipitously increased at Type 4 stage and drastically dropped afterward within both oocytes and granulosa ***,the number of differentially expressed genes between oocytes and granulosa cells dramatically increased at Type 4 stage,most of which persistently passed on to the later ***,cell communications within and between oocytes and granulosa cells became active from Type 4 stage *** dialogs connected oocytes and granulosa cells in both unidirectional and bidirectional ***2/3,TGFBR2/3,INHBA/B,and ACVR1/1B/2B of TGF-βsignaling pathway functioned in the follicle *** signaling pathway regulated the development of granulosa ***,many maternally DNA methylation-or H3K27me3-imprinted genes remained active in granulosa cells but silent in oocytes during ***,Type 4 stage is the key turning point when significant transcription changes diverge the fate of oocytes and granulosa cells,and the cell dialogs become active to assure follicle *** findings shed new insights on the transcriptome dynamics and cell dialogs facilitating the development and maturation of oocytes and follicles.

关键词： Folliculogenesis Oocyte granulosa cell Transcriptome cell dialog

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Oxidative stress in granulosa cells contributes to poor oocytequality and IVF-ET outcomes in women with polycystic ovarysyndrome

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Frontiers of Medicine 2018年第5期12卷 518-524页

作者： Qiaohong Lai Wenpei Xiang Qing Li Hanwang Zhang Yufeng Li Guijin Zhu Chengliang Xiong Lei Jin Reproductive Medicine Center Tongji Hospital Family Planning Research Institute Tongji Medical College Huazhong University ofScience and Technology Wuhan 430030 China

The increased levels of intracellular reactive oxygen species (ROS) in granulosa cells (GCs) may affect the pregnancy results in women with polycystic ovary syndrome (PCOS). In this study, we compared the in vitro fertilization and embryo transfer (IVF-ET) results of 22 patients with PCOS and 25 patients with tubal factor infertility and detected the ROS levels in the GCs of these two groups. Results showed that the PCOS group had significantly larger follicles on the administration day for human chorionic gonadotropin than the tubal factor group (P 0.05). PCOS group had slightly lower fertilization, cleavage, grade I/II embryo, clinical pregnancy, and implantation rates and higher miscarriage rate than the tubal factor group (P > 0.05). We further found a significantly higher ROS level of GCs in the PCOS group than in the tubal factor group (P cell apoptosis, which further affected the oocyte quality and reduced the positive IVF-ET pregnancy results of women with PCOS. NADPH oxidase pathway may be involved in the mechanism of ROS production in GCs of women with PCOS.

关键词： IVF-ET NADPH oxidase PCOS ROS granulosa cell

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Oleic acid reduces steroidogenesis by changing the lipid type stored in lipid droplets of ovarian granulosa cells

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Journal of Animal Science and Biotechnology 2022年第3期13卷 756-768页

作者： Xiaoge Zhou Zhaoyi Mo Yankun Li Liang Huang Sihai Yu Lan Ge Yamei Hu Shengjie Shi Lutong Zhang Liguang Wang Lei Gao Gongshe Yang Guiyan Chu Key Laboratory of Animal Genetics Breeding and Reproduction of Shaanxi ProvinceYangling 712100China Laboratory of Animal Fat Deposition&Muscle Development College of Animal Science and TechnologyNorthwest A&F UniversityYangling 712100China College of Animal Science and Technology Northwest A&F UniversityYangling 712100China College of veterinary medicine Northwest A&F UniversityYangling 712100China

Background:Oleic acid is an abundant free fatty acid present in livestock that are in a negative energy-balance state,and it may have detrimental effects on female reproduction and *** acid induces lipid accumulation in bovine granulosa cells,which leads to a foam cell-like morphology and reduced ***,why oleic acid increases lipid accumulation but decreases steroidogenesis remains *** study focused on oleic acid’s effects on lipid type and ***:Oleic acid increased the lipid accumulation in a concentration-dependent manner and mainly increased the triglyceride level and decreased the cholesterol ester *** acid also led to a decline in estradiol and progesterone production in porcine granulosa cells in *** addition,oleic acid up-regulated the expression of CD36 and diacylglycerol acyltransferase 2,but down-regulated the expression of 3-hydroxy-3-methylglutarylcoenzyme A reductase,scavenger receptor class B member 1 and acetyl-Coenzyme A acetyltransferase 2,as well as steroidogenesis-related genes,including cytochrome P450 family 11 subfamily A member 1,cytochrome P450family 19 subfamily A member 1 and 3 as well as steroidogenic acute regulatory protein at the mRNA and protein *** oleic acid-rich diet also enhanced the triglyceride levels and reduced the cholesterol levels in ovarian tissues of female mice,which resulted in lower estradiol levels than in control-fed *** with the control,decreases in estrus days and the numbers of antral follicles and corpora lutea,as well as an increase in the numbers of the atretic follicles,were found in the oleic acid-fed female ***:Oleic acid changed the lipid type stored in lipid droplets of ovarian granulosa cells,and led to a decrease in *** results improve our understanding of fertility decline in livestock that are in a negative energy-balance state.

关键词： Fertility granulosa cell Lipid droplet Oleic acid Steroidogenesis

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Effect of epidermal growth factor on follicle-stimulating hormone-induced proliferation of granulosa cells from chicken prehierarchical follicles

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第11期12卷 875-883页

作者： Jin-xing LIN Yu-dong JIA Cai-qiao ZHANG Key Laboratory of Animal Epidemic Etiology ＆ Immunological Prevention of the Ministry of Agriculture Department of Veterinary Medicine College of Animal Sciences Zhejiang University Hangzhou 310058 China

The development of ovarian follicular cells is controlled by multiple circulating and local hormones and factors, including follicle-stimulating hormone （FSH） and epidermal growth factor （EGF）. In this study, the stagespecific effect of EGF on FSH-induced proliferation of granulosa cells was evaluated in the ovarian follicles of egg-laying chickens. Results showed that EGF and its receptor （EGFR） mRNAs displayed a high expression in granulosa cells from the prehierarchical follicles, including the large white follicle （LWF） and small yellow follicle （SYF）, and thereafter the expression decreased markedly to the stage of the largest preovulatory follicle. SYF represents a turning point of EGF/EGFR mRNA expression during follicle selection. Subsequently the granulosa cells from SYF were cultured to reveal the mediation of EGF in FSH action. cell proliferation was remarkably increased by treatment with either EGF or FSH （0.1-100 ng/ml）. This result was confirmed by elevated proliferating cell nuclear antigen （PCNA） expression and decreased cell apoptosis. Furthermore, EGF-induced cell proliferation was accompanied by increased mRNA expressions of EGFR, FSH receptor, and the cell cycle-regulating genes （cyclins D1 and El, cyclin-dependent kinases 2 and 6） as well as decreased expression of luteinizing hormone receptor mRNA. However, the EGF or FSH-elicited effect was reversed by simultaneous treatment with an EGFR inhibitor AG1478. In conclusion, EGF and EGFR expressions manifested stage-specific changes during follicular development and EGF mediated FSH-induced cell proliferation and retarded cell differentiation in the prehierarchical follicles. These expressions thus stimulated follicular growth before selection in the egg-laying chicken.

关键词： Epidermal growth factor Follicle-stimulating hormone granulosa cell Proliferation Chicken

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Effects of Fenvalerate on Steroidogenesis in Cultured Rat granulosa cells

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Biomedical and Environmental Sciences 2005年第2期18卷 108-116页

作者： JIAN-FENGCHEN HAI-YANCHEN RULIU JUNHE LINSONG QIANBIAN LI-CHUNXU JIAN-WEIZHOU HANGXIAO GUI-DONGDAI XIN-RUWANG JiangsuKeyLaboratoryofAppliedToxicology NanjingMedicalUniversityNanjingJiangsu210029China

Objective This study was designed to examine the in vitro effects of fenvalerate on steroid production and steroidogenic enzymes mRNA expression level in rat granulosa cells. Methods Using primary cultured rat granulosa cells (rGCs) as model, fenvalerate of various concentrations (0, 1, 5, 25, 125, 625 μmol/L) was added to the medium for 24 h. In some cases, optimal concentrations of 22(R)-hydroxycholesterol (25 μmol/L), Follicle stimulating hormone (FSH, 2 mg/L), or 8-Bromo-cAMP (1 mmol/L) were provided. Concentrations of 17β-estradiol(E2) and progesterone (P4) in the medium from the same culture wells were measured by RIA and the steroidogenic enzyme mRNA level was quantified by semi-quantitative RT-PCR. Results Fenvalerate decreased both P4 and E2 production in a dose-dependent manner while it could significantly stimulate rGCs proliferation. This inhibition was stronger in the presence of FSH. Furthermore, it could not be reversed by 22(R)-hydroxycholesterol or 8-Bromo-cAMP. RT-PCR revealed that fenvalerate had no significant effect on 3β-HSD, but could increase the P450scc mRNA level. In addition, 17β-HSD mRNA level was dramatically reduced with the increase of fenvalerate dose after 24 h treatment. Conclusion Fenvalerate inhibits both P4 and E2 production in rGCs. These results support the view that fenvalerate is considered as a kind of endocrine-disrupting chemicals. The mechanism of its disruption may involve the effects on steroidogenesis signaling cascades and/or steroidogenic enzyme’s activity.

关键词： Endocrine disruptor Pyrethroid Steroidogenesis granulosa cell Rat

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Expression of Leptin Long-form Receptor mRNA in Luteinized granulosa cells of Obese Women with Polycystic Ovary Syndrome

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2007年第4期27卷 461-463页

作者：尹婕刘义吕立群王冬花龚成肖维盛慧 Department of Obstetrics and Gynecology Union Hospital Tongji Medical College Huazhong University of Science and Technology

To investigate the expression of mRNA of leptin long-form receptor （OB-Rb） in luteinized granulosa ceils of obese women with polycystic ovary syndrome （PCOS）, and to determine the role of leptin in the physiopathology of PCOS, luteinized granulosa cells were collected from the follicle fluid of 10 obese women who met the diagnostic criteria for PCOS and their BMI was equal to or greater than 25 kg/m^2, and at the same time, granulosa cells were collected from 10 normal women undergoing IVF-ET who served as the control group. Some luteinized granulosa cells were taken from normal women for in-vitro culture, into which human leptin of different concentrations was added （0, 10, 100 and 1000 ng/mL）. After stimulation with leptin for 48 h, RT-PCR was employed for the detection of the expression of OB-RLInRNA in the luteinized granulosa cells. Our results showed that the level of OB-RLmRNA in luteinized granulosa cells of obese PCOS women was higher than those in the control （P〈0.05）. In luteinized granulosa cells cultured in vitro and stimulated by human leptin for 48 h, the level of OB-RLmRNA was higher than those without leptin stimulation （P〈0.01）, and when leptin concentration was at 100 ng/mL, and the level of OB-RLmRNA reached a peak, It is concluded that in obese PCOS women, the level of serum leptin is increased, which promotes the expression of OB-RL in luteinized granulosa cells and increases the sensitivity of the granulosa cells to leptin. Leptin may contribute to anovulation in obese women with PCOS.

关键词： polycystic ovary syndrome leptin leptin receptor granulosa cell

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Apoptosis and Expression of Protein TRAIL in granulosa cells of Rats with Polycystic Ovarian Syndrome

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2007年第3期27卷 311-314页

作者：张娟朱桂金王昕荣徐蓓胡琳莉 Reproductive Medical Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The relationship between apoptosis of granulosa cells and follicle development arrest in polycystic ovarian syndrome (PCOS) rats, and the contribution of tumor necrosis factor related apoptosis inducing ligand (TRAIL) in apoptosis of granulosa cells were explored. By using sodium prasterone sulfate rat PCOS model was induced. The apoptosis of granulosa cells in ovaries of rats was observed by TdT-mediated dUTP-biotin nick end-labeling (TUNEL), and the expression of TRAIL protein and mRNA in granulosa cells was detected by using immunhistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) respectively. The apoptotic rate and the expression of protein TRAIL in granulosa cells were significantly higher in antral follicles from the PCOS rats than in those from the control rats (Pgranulosa cells of preantral follicles between the PCOS rats and the control rats (P>0.05). No apoptosis and the expression of TRAIL protein in granulosa cells of primordial follicles were found in the two groups. The expression of TRAIL mRNA was significantly stronger in granulosa cells from the PCOS rats than in those from the con- trol rats (Pgranulosa cells was significantly higher in antral follicle from the PCOS rats than in those from the control rats. TRAIL played a role in regu- lating the apoptosis of granulosa cells in PCOS rats.

关键词： tumor necrosis factor related apoptosis inducing ligand granulosa cell apoptosis polycystic ovarian syndrome rat

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Effect of vitamin D3 on production of progesterone in porcine granulosa cells by regulation of steroidogenic enzymes

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The Journal of Biomedical Research 2016年第3期30卷 203-208页

作者： So-Hye Hong Jae-Eon Lee Hong Sung Kim Young-Jin Jung DaeYoun Hwang Jae Ho Lee Seung Yun Yang Seung-Chul Kim Seong-Keun Cho Beum-Soo An Department of Biomaterials Science College of Natural Resources & Life Science Pusan National University Miryang 50463 Korea Department of Obstetrics and Gynecology Biomedical Research Institute Pusan National University School of Medicine Busan 46269 Korea Department of Animal Science College of Natural Resources & Life Science Pusan National UniversityMiryang 50463 Korea

1,25-dihydroxyvitamin D3 （VD3）, an active form of Vitamin D, is photosynthesized in the skin of vertebrates in response to solar ultraviolet B radiation （UV-B）. VD3 deficiency can cause health problems such as immune disease, metabolic disease, and bone disorders. It has also been demonstrated that VD3 is involved in reproductive functions. Female sex hormones such as estrogen and progesterone are biosynthesized mainly in ovarian granulosa cells as the ovarian follicle develops. The functions of sex hormones include regulation of the estrus cycle and puberty as well as maintenance of pregnancy in females. In this study, we isolated granulosa cells from porcine ovaries and cultured them for experiments. To examine the effects of VD3 on ovarian granulosa cells, the mRNA and protein levels of genes were analyzed by Real-time PCR and Western blotting assay. Production of progesterone from granulosa cells was also measured by ELISA assay. As a result, transcriptional and translational regulation of progesterone biosynthesis-related genes in granulosa cells was significantly altered by VD3. Furthermore, progesterone concen- trations in porcine granulosa cell-cultured media decreased in response to VD3. These results show that VD3 was a strong regulator of sex steroid hormone production in porcine granulosa cells, suggesting that vitamin D deficiency may result in inappropriate sexual development of industrial animals and eventually economic loss.

关键词： Vitamin D3 steroidogenesis progesterone granulosa cell pig

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