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Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第10期12卷 796-804页

作者： Lei LI Fang LE Li-ya WANG Xiang-rong XU Hang-ying LOU ying-ming zheng Jiang-zhong SHENG He-feng HUANG Fan JIN Centre of Reproductive Medicine Women＇s Hospital School of Medicine Zhejiang University Hangzhou 310006 China Department of Gynecologic Oncology Henan Cancer Hospital Zhengzhou 450003 China Department of Cell Biology School of Medicine Zhejiang University Hangzhou 310006 China

An association between assisted reproductive technology （ART） and neurobehavioral imprinting disorders has been reported in many studies, and it seems that ART may interfere with imprint reprogramming. However, it has never been explored whether epigenetic erros or imprinting disease susceptibility induced by ART can be inherited transgenerationally. Hence, the aim of this study was to determine the effect of in vitro fertilization and embryo transfer （IVF-ET） on transgenerational inheritance in am inbred mouse model. Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations. Their behavior, morphology, histology, and DNA methylation status at several important differentially methylated regions （DMRs） were analyzed by Morris water maze, hematoxylin and eosin （H＆E） staining, and bisulfite genomic sequencing. No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF （F1） and female and male line F2 and F3 generations. A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation （0.40±0.118, P=0.086）. Methylation status in H19/Igf2 DMR island 1, Igf2 DMR, KvDMR, and Snrpn DMR displayed normal patterns. Methylation percentage did not differ significantly from that of adults conceived naturally, and the expression of the genes they regulated was not disturbed. Transgenerational integrity, such as behavior, morphology, histology, and DNA methylation status, was maintained in these generations, which indicates that exposure of female germ cells to hormonel stimulation and gamete manipulation might not affect the individuals and their descendents.

关键词： Differentially methylated regions (DMRs), In vitro fertilization and embryo transfer (IVF-ET), Centralnervous system (CNS), Neurobe havioral imprinting disorders, Transgenerational epigenetic inheritance

Persistence and intergenerational transmission of differentially expressed genes in the testes of intracytoplasmic sperm injection conceived mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第5期14卷 372-381页

作者： Li-ya WANG Ning WANG Fang LE Lei LI Le-jun LI Xiao-zhen LIU ying-ming zheng Hang-ying LOU Xiang-rong XU Xiao-ming ZHU Yi-min ZHU He-feng HUANG Fan JIN Key Laboratory of Reproductive Genetics (Zhejiang) Ministry of Educationand Centre of Reproductive Medicine Women's HospitalSchool of MedicineZhejiang University Department of Gynecologic Oncology Henan Cancer Hospital

Intracytoplasmic sperm injection (ICSI) is commonly used to solve male infertility problems. Previous studies showed that early environmental exposure of an embryo may influence postnatal development. To detect whether ICSI operations affect the reproductive health of a male or his offspring, we established assisted reproductive technologies (ART) conceived mouse models, and analyzed gene expression profiles in the testes of both ICSI and naturally conceived (NC) newborn F1 mice using micro-array analysis. Among the differentially expressed genes, we focused on the expression of eight male reproduction-related genes. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to analyze the expression of these genes in the testes of both adult and old F1 generation mice and adult F2 generation mice. Our results showed that down-regulated and somatic cell-expressed genes in newborn mice retained their differential expression patterns in adult and old F1 generation individuals, implying the persistence and fetal origin of the alteration in the expression of these genes. The intergenerational transmission of differential gene expression was observed, but most changes tended to be reduced in adult F2 generations. Controlled ovarian hyperstimulation (COH) and in vitro fertilization (IVF) mice models were added to explore the precise factors contributing to the differences in ICSI offspring. The data demonstrated that superovulation, in vitro culture, and mechanical stimulation involved in ICSI had a cumulative effect on the differential expression of these male reproductive genes.

关键词： Intracytoplasmic sperm injection Testis Intergenerational transmission

Hyper-CVAD chemotherapy or autologous stem cell transplantation in patients with peripheral T cell lymphomas： a single centre report

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Chinese Medical Journal 2012年第22期125卷 4134-4137页

作者： XU Yang WU Xiao-jin WANG ying JIN zheng-ming SUN Ai-ning WU De-pei Soochow Univ Affiliated Hosp 1 Jiangsu Inst Hematol Key Lab Thrombosis & HemostasisMinist Hlth Suzhou 215006 Jiangsu Peoples R China

Background Peripheral T-cell lymphoma （PTCL） is generally characterized by poor prognosis after conventional chemotherapy. The place for high-dose chemotherapy and autologous stem cell transplantation （ASCT） in these patients is still not clear. In this study, we presented the outcomes of PTCL patients followed these treatments in our centre. Methods We retrospectively analyzed the outcomes of 39 patients with PTCL received the two treatments between 1999 and 2010. Results The 3-year overall survival （OS） of 61.9% and 3-year progression free survival （PFS） of 35.7% were observed in the 39 patient. Twenty-one patients received Hyper-CVAD chemotherapy with 3-year OS of 46.2% and 3-year PFS of 27.9%. Eighteen patients received ASCT with 3-year OS of 70.3% and 3-year PFS of 44.2%. Further analysis revealed that patients with elevated lactate dehydrogenase, at least 2 international prognostic index （IPI） points, and extranodal involvement had a poorer outcome compared with the control group. Conclusion These findings might suggest that Hyper-CVAD chemotherapy and ASCT could offer a durable survival benefit for patients with aggressive PTCL.

关键词： peripheral T-cell lymphoma hyper-CVAD chemotherapy autologous stem cell transplantation

Significant alterations in the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology

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Significant alterations in the frequency of trinucleotide re...

Different sperm sources and parameters can influence intracytoplasmic sperm injection outcomes before embryo implantation

第十二次全国医学遗传学学术会议

作者： ying-ming zheng Li Li Kai Yan Song-Chang Chen Chen-ming Xu Fan Jin Department of Reproductive Endocrinology Women's HospitalZhejiang University School of Medicine Key Laboratory of Reproductive Genetics National Ministry of Education(Zhejiang University)Women's Reproductive Healthy Laboratory of Zhejiang Province

Background This study investigates possible changes in the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology(ART) in comparison with matched controls from spontaneous *** A prospective clinical observational study was performed on two hundred and forty-six families recruited from the in vitro fertilisation centre at a tertiary-care,university-affiliated,teaching ***,peripheral and umbilical cord blood samples were collected and the trinucleotide repeat dynamic mutation genes of ATN1,AR,ATXN1,ATXN3,Huntington,DMPK and FMR-1 were investigated between *** frequencies and sizes of the mutational repeats of intergenerational instability were *** A total of 2,466 transmissions were identified in ART offspring,with 2.11%(n=52/2,466) of alleles being unstable upon transmission. In the control group,the frequency of dynamic mutation was 0.77%(n=10/1,300).Stati 0.05).The repeat copy numbers of examined genes in all parents and their babies were found to be within the normal *** Our results illustrated that more significant alterations in the frequency of trinucleotide repeat dynamic mutations in offspring conceived through *** studies determining the factors that influence instability of genome in ART procedure are urgently needed.

关键词： assisted reproductive technology offspring dynamic mutation trinucleotide repeat

来源： cnki会议评论

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第1期13卷 1-10页

作者： Yue-hong LU1,2, Hui-juan GAO1, Bai-jia LI1, ying-ming zheng1, ying-hui YE1, Yu-li QIAN1, Chen-ming XU1, He-feng HUANG1, Fan JIN1 (1Department of Reproductive Endocrinology, Key Laboratory of Reproductive Genetics, Ministry of Education, and Key Laboratory of Women’s Reproductive Health of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China) (2Department of Reproductive Health, Shaoxing Women and Children Hospital, Shaoxing 312000, China) Department of Reproductive Endocrinology Key Laboratory of Reproductive Genetics Ministry of Education and Key Laboratory of Women's Reproductive Health of Zhejiang Province Women's Hospital School of Medicine Zhejiang University Hangzhou 310006 China

To evaluate the effects of sperm with different parameters and sources on the outcomes of intracytoplasmic sperm injection (ICSI), 1972 ICSI cycles were analyzed retrospectively. Groups 1 to 5 were composed of cycles using ejaculated sperm and were grouped according to sperm quantity, quality, and morphology into normal (288 cycles), or mild (329 cycles), moderate (522 cycles), severe (332 cycles), and extremely severe (171 cycles) oligozoospermia and/or asthenozoospermia and/or teratozoospermia (OAT) groups. Group 6 was composed of 250 cycles using testicular or epididymal sperm, and Group 7 consisted of 80 cycles using frozen-thawed sperm. We found that fertilization rates were gradually reduced from Groups 1 to 6, and reached statistical difference in Groups 5 and 6 (P0.05). A total of nine cases of malformation were observed, with a malformation rate of 1.25% (9/719). In conclusion, different sperm sources and parameters can affect ICSI outcomes before embryo implantation. A full assessment of offspring mal-formation will require further study using a larger sample size.

关键词： Intracytoplasmic sperm injection (ICSI)i Sperm Sperm source Sperm parameters Malformation

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实时Web图形应用中的选择性场景传输

计算机集成制造系统 2006年第4期12卷 636-640页

作者：唐敏英正明 CHOU Shang-ching 董金祥浙江大学CAD&CG国家重点实验室浙江杭州310027 Wichita州立大学计算机系勘萨斯州威奇托67220

为了解决实时Web图形应用中大型场景数据传输所需时间长的问题,提出一种选择性场景传输算法。通过对需要传输的模型和纹理信息的最终显示贡献进行定量分析,给出了每个对象或每个面片的视觉重要性的度量,并在此基础上设计了选择性传输场... 详细信息

为了解决实时Web图形应用中大型场景数据传输所需时间长的问题,提出一种选择性场景传输算法。通过对需要传输的模型和纹理信息的最终显示贡献进行定量分析,给出了每个对象或每个面片的视觉重要性的度量,并在此基础上设计了选择性传输场景中模型和纹理的算法,给出了基于图形硬件绘制方法的实现。原型系统的实验结果表明,该方法可以在保持用户图形质量的同时减少等待时间,并作为一个有力的工具来提升实时Web图形应用的性能。

关键词：实时Web图形应用场景传输层次细节渐进网格

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新型便携式扬声器系统

电声技术 2005年第5期29卷 23-24页

作者：应正铭

近年来,传统的立体声系统正在逐渐失去市场,传统的立体声分体式设备和音箱的销售已急剧下降.虽然人们仍在欣赏音乐,但用传统的立体声音响系统播放CD,MD,磁带和LP已经不能满足人们的需求了.如今音乐爱好者们需要的是可更方便地与音乐播... 详细信息

近年来,传统的立体声系统正在逐渐失去市场,传统的立体声分体式设备和音箱的销售已急剧下降.虽然人们仍在欣赏音乐,但用传统的立体声音响系统播放CD,MD,磁带和LP已经不能满足人们的需求了.如今音乐爱好者们需要的是可更方便地与音乐播放器连接和操作的音箱,如便携式硬盘播放器、闪存播放器、便携式数字卫星接收器及家居无线网络.另外,有移动使用需求的消费者要求音箱可以适应他们设备的便携性.这样小而轻的有源音箱系统的市场机遇就显现出来了.而且厂家现可采用几种新的低成本技术极大地改善扬声器的效率和音质.

关键词：便携式扬声器系统立体声音响系统立体声系统音乐播放器硬盘播放器传统分体式音箱 MD

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

Different sperm sources and parameters can influence intracytoplasmic sperm injection outcomes before embryo implantation

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第5期14卷 381-381页

作者： Yue-hong LU Hui-juan GAO Bai-jia LI ying-ming zheng ying-hui YE Yu-li QIAN Chen-ming XU He-feng HUANG Fan JIN

To evaluate the effects of sperm with different parameters and sources on the outcomes of intracytoplasmic sperm injection (ICSI), 1972 ICSI cycles were analyzed retrospectively. Groups 1 to 5 were composed of cycles using ejaculated sperm and were grouped according to sperm quantity, quality, and morphology into normal (288 cycles), or mild (329 cycles), moderate (522 cycles), severe (332 cycles), and extremely severe (171 cycles) oligozoospermia and/or asthenozoospermia and/or teratozoospermia (OAT) groups. Group 6 was composed of 250 cycles using testicular or epididymal sperm, and Group 7 consisted of 80 cycles using frozen-thawed sperm. We found that fertilization rates were gradually reduced from Groups 1 to 6, and reached statistical difference in Groups 5 and 6 (P0.05). A total of nine cases of malformation were observed, with a malformation rate of 1.25% (9/719). In conclusion, different sperm sources and parameters can affect ICSI outcomes before embryo implantation. A full assessment of offspring malformation will require further study using a larger sample size.

关键词：胚胎植入显微注射精子低出生体重胞浆 ICSI 畸形率循环使用