Shanghai Key Laboratory for Reproductive Medicine

Shanghai, China

Shanghai Key Laboratory for Reproductive Medicine

Shanghai, China

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Fan Y.-X.,Shanghai JiaoTong University | Song J.,CAS Tianjin Institute of Industrial Biotechnology | Song J.,Monash University | Xu C.,Shanghai JiaoTong University | And 3 more authors.
Current Bioinformatics | Year: 2013

Protein signal peptides play a vital role in targeting and translocation of most secreted proteins and many integral membrane proteins in both prokaryotes and eukaryotes. Consequently, accurate prediction of signal peptides and their cleavage sites is an important task in molecular biology. In the present study, firstly, we develop a novel discriminative scoring method for classifying proteins with or without signal peptides. This method successfully captured the characteristics of signal peptides and non-signal peptides by integrating hydrophobicity alignment and positionspecific amino acid propensities based on the highest average positions. As a result, this method is capable of discriminating proteins with signal peptides at the overall accuracies of 96.3%, 97.0% and 97.2% by leave-one-out jackknife tests on the constructed benchmark datasets for three different organisms, i.e. Eukaryotic, Gram-negative, and Gram-positive respectively. Secondly, we consider the prediction task of signal peptide cleavage sites as a sequence labeling problem and apply Conditional Random Fields (CRFs) algorithm to solve it. Experimental results demonstrate that the proposed CRFs-based cleavage site finding approach can achieve the prediction success rates of 80.8%, 89.4%, and 74.0% respectively, for the secretory proteins from three different organisms. An online tool, LnSignal, is established for labeling the N-terminal signal cleavage sites and is freely available for academic use at http://www.csbio.sjtu.edu.cn/bioinf/LnSignal. © 2013 Bentham Science Publishers.


Bao J.,Shanghai JiaoTong University | Wu J.,Shanghai JiaoTong University | Wu J.,Shanghai Key Laboratory for Reproductive Medicine | Schuster A.S.,Shanghai JiaoTong University | And 2 more authors.
Biology of Reproduction | Year: 2013

In mammals, the transcriptome of large noncoding RNAs (lncRNAs) is believed to be greater than that of messenger RNAs (mRNAs). Some lncRNAs, especially large intergenic noncoding RNAs (lincRNAs), participate in epigenetic regulation by binding chromatin-modifying protein complexes and regulating proteincoding gene expression. Given that epigenetic regulation plays a critical role in male germline development, we embarked on expression profiling of both lncRNAs and mRNAs during male germline reprogramming and postnatal development using microarray analyses. We identified thousands of lncRNAs and hundreds of lincRNAs that are either up-or downregulated at six critical time points during male germ cell development. In addition, highly regulated lncRNAs were correlated with nearby (< 30 kb) mRNA gene clusters, which were also significantly upor downregulated. Large ncRNAs can be localized to both the nucleus and cytoplasm, with nuclear lncRNAs mostly associated with key components of the chromatin-remodeling protein complexes. Our data indicate that expression of lncRNAs is dynamically regulated during male germline development and that lncRNAs may function to regulate gene expression at both transcriptional and posttranscriptional levels via genetic and epigenetic mechanisms. © 2013 by the Society for the Study of Reproduction, Inc.


Zhang A.,Shanghai JiaoTong University | Zhang A.,Shanghai Key Laboratory for Reproductive Medicine | Xu B.,Shanghai JiaoTong University | Sun Y.,Shanghai JiaoTong University | And 6 more authors.
Journal of Assisted Reproduction and Genetics | Year: 2012

Purpose To investigate the effect of human cumulus cells on the maturation and developmental potential of immature oocytes in ICSI cycles. Methods Immature oocytes were randomly divided into two groups: the cumulus-denuded oocyte group (group A) and the cumulus-intact oocyte group (group B). Only oocytes that reached metaphase II (MII) stage after in vitro maturation were used in the ICSI procedure. In vivo mature sibling MII oocytes served as the control group. Maturation rate, fertilization rate, embryo quality and developmental potential were examined. Results There was no significant difference in maturation rate between group A (68.16%) and group B (70.49%; P>0.05). The total fertilization rate among the three groups was comparable (P>0.05), while the zygotes with two pronuclei in group A (74.59%) or group B (75.97%) were significantly lower than those in control group (84.29%; P<0.05). The available embryo rate in group A (11.49%) was markedly lower than that in group B (27.66%; P<0.05), and both of them were significantly lower than that in control group (62.38%; P<0.05). The proportion of = 6-cell embryos in group B (45.74%) was notably higher than in group A (26.44%; P<0.05), and both were markedly lower than in control group (65.92%; P<0.05). The proportion of embryos with <10% fragmentation in group A (13.79%) was significantly lower than in group B (29.79%; P<0.05), and both were notably lower than in control group (42.98%; P<0.05). Conclusions The presence of cumulus cells surrounding the immature oocytes during IVM before ICSI had no influence on nuclear maturation and fertilization, but leads to better subsequent embryonic development. This is perhaps mediated by an improvement in cytoplasmic maturation. © 2012 Springer Science+Business Media, LLC.


Ding X.-M.,Shanghai JiaoTong University | Pan X.-Y.,Shanghai JiaoTong University | Xu C.,Shanghai JiaoTong University | Xu C.,Shanghai Key Laboratory for Reproductive Medicine | Shen H.-B.,Shanghai JiaoTong University
Current Computer-Aided Drug Design | Year: 2010

The interaction between DNA and proteins comprises a pivotal role in almost every cellular process, including gene regulation and DNA replication. Given a protein, it is very important to know whether it is a DNA-binding protein or not and where the binding sites are. Over the last three decades, since the discovery that lac operon was regulated by a protein, knowledge of the DNA-protein interactions has soared. However, it is very difficult to use experimental techniques to identify the DNA-binding proteins because these experiments can be prohibitively labor-intensive in studying all the possible mutations of the residues on the molecular surface. Hence, it has been generally recognized that the ability to automatically identify the DNA binding proteins and their binding sites can significantly speed up our understanding of cellular activities and contribute to advances in drug discovery. The main goal of present paper is to review the recent progress in the development of computational approaches to predict DNA-protein bindings. We will show a historical roadmap of the amelioration, and how the modifications promote better performance. © 2010 Bentham Science Publishers Ltd.


Bao J.,University of Nevada, Reno | Bao J.,Shanghai JiaoTong University | Bao J.,Shanghai Key Laboratory for Reproductive Medicine | Wu Q.,University of Nevada, Reno | And 6 more authors.
Molecular and Cellular Endocrinology | Year: 2011

We identified Ran-binding protein 17 (RANBP17) as one of the interacting partners of sperm maturation 1 (SPEM1) using yeast 2-hybrid screening and immunoprecipitation assays. Expression profiling analyses suggested that RANBP17 was preferentially expressed in the testis. Immunofluorescent confocal microscopy revealed a dynamic localization pattern of RANBP17 during spermatogenesis. In primary spermatocytes RANBP17 was mainly localized to the XY body. In the subsequent spermiogenesis, RANBP17 was first observed in the nuclei of round spermatids (steps 1-7) and then confined to the manchette of elongating spermatids (steps 8-14) together with its interacting partner SPEM1. In the Spem1-null testes, levels of RANBP17 were significantly elevated. As a member of a large protein family involved in the nucleocytoplasmic transport, RANBP17 may have a role in sex chromosome inactivation during the meiotic phase of spermatogenesis, and also in the intramanchette transport during spermiogenesis. Interactions between RANBP17 and SPEM1, for the first time, point to a potential function of SPEM1 in the RANBP17-mediated nucleocytoplasmic transport. © 2010 Elsevier Ireland Ltd.


Lu Z.-M.,Shanghai JiaoTong University | Lu Z.-M.,Anhui Medical University | Wang M.,Shanghai JiaoTong University | Wang M.,Shanghai Key Laboratory for Reproductive Medicine | And 2 more authors.
Acta Anatomica Sinica | Year: 2011

Objective: To determine the feasibility of pcDNA3.1/mESP as a potential immunocontraceptive antigen. Methods: Eukaryotic expression plasmid pcDNA3.1/mESP, encoding N-terminal of mouse sperm equatorial segment protein (mESP), was constructed. Two groups of mice (n = 8/group) were inoculated with plasmids of pcDNA3.1/mESP and pcDNA3.1 respectively. RT-PCR, ELISA and double immunofluorescence assay were performed to observe pcDNA3.1/mESP expression and immune response in the inoculated mice. Mouse mating test was employed to study fertility of the experimental and control group. Results: mESP cDNA positive band was detected in muscle from mice immunized with pcDNA3.1/mESP, which identified the expression of the recombinant plasmid. The pcDNA3.1/mESP induced specific antibody against mESP in the experimental mice. Significant difference of mean litter size between experimental and control groups was observed, while the rate of fertility did not decrease. Conclusion: This study indicates the need to strengthen DNA vaccines in order to obtain effective immunocontraception.


Lu M.,Shanghai JiaoTong University | Lu M.,Anhui Medical University | Lu M.,Shanghai Key Laboratory for Reproductive Medicine | Tian H.,Shanghai JiaoTong University | And 9 more authors.
Cell Death and Disease | Year: 2015

Long non-coding RNAs (lncRNAs), which are extensively transcribed from the genome, have been proposed to be key regulators of diverse biological processes. However, little is known about the role of lncRNAs in regulating spermatogenesis in human males. Here, using microarray technology, we show altered expression of lncRNAs in the testes of infertile men with maturation arrest (MA) or hypospermatogenesis (Hypo), with 757 and 2370 differentially down-regulated and 475 and 163 up-regulated lncRNAs in MA and Hypo, respectively. These findings were confirmed by quantitative real-time PCR (qRT-PCR) assays on select lncRNAs, including HOTTIP, imsrna320, imsrna292 and NLC1-C (narcolepsy candidate-region 1 genes). Interestingly, NLC1-C, also known as long intergenic non-protein-coding RNA162 (LINC00162), was down-regulated in the cytoplasm and accumulated in the nucleus of spermatogonia and primary spermatocytes in the testes of infertile men with mixed patterns of MA compared with normal control. The accumulation of NLC1-C in the nucleus repressed miR-320a and miR-383 transcript and promoted testicular embryonal carcinoma cell proliferation by binding to Nucleolin. Here, we define a novel mechanism by which lncRNAs modulate miRNA expression at the transcriptional level by binding to RNA-binding proteins to regulate human spermatogenesis. © 2015 Macmillan Publishers Limited. All rights reserved.


Bao J.,Shanghai JiaoTong University | Bao J.,Shanghai Key Laboratory for Reproductive Medicine | Bao J.,University of Nevada, Reno | Zhang J.,Shenyang University | And 4 more authors.
Molecular and Cellular Endocrinology | Year: 2010

Spermiogenesis represents the process through which haploid male germ cells differentiate from round spermatids into elongated spermatids and eventually the male gametes called spermatozoa. Haploid cell differentiation is unique to male germ cell development and many unique genes/proteins essential for this process have been discovered. SPEM1 is one of these spermiogenesis-essential proteins encoded by a testis-specific gene exclusively expressed in the developing spermatids. Inactivation of Spem1 in mice results in deformed spermatozoa characterized by " head-bent-back" abnormalities with 100% penetrance. Using yeast two-hybrid screening assays, we identified UBQLN1 as one of the SPEM1-interacting partners. UBQLN1 and SPEM1 were colocalized to the manchette of elongating spermatids. Since UBQLN1 functions through binding and directing poly-ubiquitinated proteins to the proteasome for degradation, interactions between UBQLN1 and SPEM1 suggest a role in the regulation of protein ubiquitination during spermiogenesis. © 2010 Elsevier Ireland Ltd.


Yang F.,Shanghai JiaoTong University | Xu Y.-Y.,Shanghai JiaoTong University | Wang S.-T.,Jiangnan University | Shen H.-B.,Shanghai JiaoTong University | Shen H.-B.,Shanghai Key Laboratory for Reproductive Medicine
Neurocomputing | Year: 2014

The reproductive system is a specific system of organs working together for the purpose of reproduction. As one of the most significant characteristics of human cell, subcellular localization plays a critical role for understanding specific functions of mammalian proteins. In this study, we developed a novel computational protocol for predicting protein subcellular locations from microscope images of cells in human reproductive tissues. Three major steps are contained in this protocol, i.e., protein object identification, image feature extraction, and classification. We first separated protein and DNA staining in the images with both linear and non-negative matrix factorization separation methods; then we extracted protein multi-view global and local texture features including wavelet Haralick, local binary patterns, local ternary patterns, and the local quinary patterns; finally based on the selected important feature subset, we constructed an ensemble classifier with support vector machines for classifications. Experiments are performed on a benchmark dataset consisting of seven major subcellular classes in human reproductive tissues collected from human protein atlas. Our results show that the local texture pattern features play an important complementary role to global features for enhancing the prediction performance. An overall accuracy of 85% is obtained through current system, and when only confident classifications are considered, the accuracy can reach 99%. It is the first developed image based protein subcellular location predictor specifically for human reproductive tissue. The promising results indicate that the developed protocol can be applied for accurate large-scale protein subcellular localization annotations in human reproductive system. © 2013 Elsevier B.V.

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