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11
result(s) for
"生殖细胞发育"
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MIWI and piRNA-mediated cleavage of messenger RNAs in mouse testes
by
Peng Zhang Jun-Yan Kang Lan-Tao GOU Jiajia Wang Yuanchao Xue Geir Skogerboe Peng Dai Da-Wei Huang Runsheng Chen Xiang-Dong Fu Mo-Fang Liu Shunmin He
in
3' Untranslated Regions
,
631/1647/2217/2018
,
631/337/384
2015
The piRNA machinery is known for its role in mediating epigenetic silencing of transposons. Recent studies suggest that this function also involves piRNA-guided cleavage of transposon-derived transcripts. As many piRNAs also appear to have the capacity to target diverse mRNAs, this raises the intriguing possibility that piRNAs may act extensively as siRNAs to degrade specific mRNAs. To directly test this hypothesis, we compared mouse PIWI (MI- WI)-associated piRNAs with experimentally identified cleaved mRNA fragments from mouse testes, and observed cleavage sites that predominantly occur at position 10 from the 5' end of putative targeting piRNAs. We also noted strong biases for U and A residues at nucleotide positions 1 and 10, respectively, in both piRNAs and mRNA frag- ments, features that resemble the pattern of piRNA amplification by the 'ping-pong' cycle. Through mapping of MIWI-RNA interactions by CLIP-seq and gene expression profiling, we found that many potential piRNA-targeted mRNAs directly interact with MIWI and show elevated expression levels in the testes of Miwi catalytic mutant mice. Reporter-based assays further revealed the importance of base pairing between piRNAs and mRNA targets and the requirement for both the slicer activity and piRNA-loading ability of MIWI in piRNA-mediated target repression. Importantly, we demonstrated that proper turnover of certain key piRNA targets is essential for sperm formation. Together, these findings reveal the siRNA-like function of the piRNA machinery in mouse testes and its central requirement for male germ cell development and maturation.
Journal Article
Atg7 is required for acrosome biogenesis during spermatogenesis in mice
by
Hongna Wang Haifeng Wan Xixia Li Weixiao Liu Qi Chen Yaqing Wang Lin Yang Hongmei Tang Xiujun Zhang Enkui Duan Xiaoyang Zhao Fei Gao Wei Li
in
631/136/2434/1822
,
631/80/39
,
631/80/642/1624
2014
The acrosome is a specialized organelle that covers the anterior part of the sperm nucleus and plays an essential role in the process of fertilization. The molecular mechanism underlying the biogenesis of this lysosome-related organelle (LRO) is still largely unknown. Here, we show that germ cell-specific Atg7-knockout mice were infertile due to a defect in aerosome biogenesis and displayed a phenotype similar to human globozoospermia; this reproductive defect was successfully rescued by intracytoplasmic sperm injections. Furthermore, the depletion of Atg7 in germ cells did not affect the early stages of development of germ cells, but at later stages of spermatogenesis, the proacroso- mal vesicles failed to fuse into a single acrosomal vesicle during the Golgi phase, which finally resulted in irregular or nearly round-headed spermatozoa. Autophagic flux was disrupted in Atg7-depleted germ cells, finally leading to the failure of LC3 conjugation to Golgi apparatus-derived vesicles. In addition, Atg7 partially regulated another giobozo- ospermia-related protein, Golgi-associated PDZ- and coiled-coil motif-containing protein (GOPC), during acrosome biogenesis. Finally, the injection of either autophagy or lysosome inhibitors into testis resulted in a similar phenotype to that of germ cell-specific AtgT-knockout mice. Altogether, our results uncover a new role for Atg7 in the biogenesis of the acrosome, and we provide evidence to support the autolysosome origination hypothesis for the acrosome.
Journal Article
DNA methylation and chromatin accessibility profiling of mouse and human fetal germ cells
by
Hongshan Guo Boqiang Hu Liying Yan Jun Yong Yan Wu Yun Gao Fan Guo Yu Hou Xiaoying Fan Ji Dong Xiaoye Wang Xiaohui Zhu Jie Yan Yuan Wei Hongyan Jin Wenxin Zhang Lu Wen FuchouTang Jie Qiao
in
631/136/532/2435
,
631/208/176/1988
,
631/337/100
2017
Chromatin remodeling is important for the epigenetic reprogramming of human primordial germ cells. However, the comprehensive chromatin state has not yet been analyzed for human fetal germ ceils (FGCs). Here we use nucleosome occupancy and methylation sequencing method to analyze both the genome-wide chromatin accessibility and DNA methylome at a series of crucial time points during fetal germ cell development in both human and mouse. We find 116 887 and 137 557 nucleosome-depleted regions (NDRs) in human and mouse FGCs, covering a large set of germline-specific and highly dynamic regulatory genomic elements, such as enhancers. Moreover, we find that the distal NDRs are enriched specifically for binding motifs of the pluripotency and germ cell master regulators such as NANOG, SOX17, AP2γ and OCT4 in human FGCs, indicating the existence of a delicate regulatory balance between pluripotency-related genes and germ cell-specific genes in human FGCs, and the functional significance of these genes for germ cell development in vivo. Our work offers a comprehensive and high-resolution roadmap for dissecting chromatin state transition dynamics during the epigenomic reprogramming of human and mouse FGCs.
Journal Article
Mouse models in male fertility research
2011
Limited knowledge of the genetic causes of male infertility has resulted in few treatment and targeted therapeutic options. Although the ideal approach to identify infertility causing mutations is to conduct studies in the human population, this approach has progressed slowly due to the limitations described herein. Given the complexity of male fertility, the entire process cannot be modeled in vitro. As such, animal models, in particular mouse models, provide a valuable alternative for gene identification and experimentation. Since the introduction of molecular biology and recent advances in animal model production, there has been a substantial acceleration in the identification and characterization of genes associated with many diseases, including infertility. Three major types of mouse models are commonly used in biomedical research, including knockoutJknockin/gene-trapped, transgenic and chemical-induced point mutant mice. Using these mouse models, over 400 genes essential for male fertility have been revealed. It has, however, been estimated that thousands of genes are involved in the regulation of the complex process of male fertility, as many such genes remain to be characterized. The current review is by no means a comprehensive list of these mouse models, rather it contains examples of how mouse models have advanced our knowledge of post-natal germ cell development and male fertility regulation.
Journal Article
RNA binding proteins in spermatogenesis: an in depth focus on the Musashi family
by
Jessie M Sutherland Nicole A Siddall Gary R Hime Eileen A McLaughlin
in
Animals
,
Binding proteins
,
Cytoplasm
2015
Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactive transcription despite heavy translational requirements for continued growth and differentiation. Hence, spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation of gene expression, facilitated by RNA binding proteins (RBPs), which remain abundantly expressed throughout this process. One such group of proteins is the Musashi family, previously identified as critical regulators of testis germ cell development and meiosis in Drosophila, and also shown to be vital to sperm development and reproductive potential in the mouse. This review describes the role and function of RBPs our recent knowledge of the Musashi proteins in spermatogenesis. within the scope of male germ cell development, focusing on The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted. We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis. This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.
Journal Article
The role of cysteine-rich secretory proteins in male fertility
by
Adam J Koppers Thulasimala Reddy Moira K O'Bryan
in
Animals
,
Epididymis - metabolism
,
Fertility - physiology
2011
The cysteine-rich secretory proteins (CRISPs) are a subgroup of the CRISP, antigen 5 and Pr-1 (CAP) protein superfamily, and are found only in vertebrates. They show a strong expression bias to the mammalian male reproductive tract and the venom of poisonous reptiles. Within the male reproductive tract CRISPs have been implicated in many aspects of male germ cell biology spanning haploid germ cell development, epididymal maturation, capacitation, motility and the actual processes of fertilization. At a structural level, CRISPs are composed of two domains, a CAP domain, which has been implicated in cell-cell adhesion, and a CRISP domain, which has been shown to regulate several classes of ion channels across multiple species. Herein, we will review the current literature on the role of CRISPs in male fertility, and by inference to related non-mammalian protein, infer potential biochemical functions.
Journal Article
Expression of vasa Gene in Development Process of Germ Cells in Male Rat
2016
In order to explore the role of vasa gene in the development of germ cells after gonad differentiation in male rats,the expression of vasa mRNA and vasa protein in 17.5-day-old fetal rats and neonatal rats was detected by real-time fluorescent quantitative PCR and immunohistochemistry method.The results showed that the expression of vasa mRNA was detected in the testis tissue of 17.5-day-old fetal rats and neonatal rats,and the expression of vasa mRNA in testis of neonatal rats was high than that in fetal rats.The expression of vasa protein was detected in neonatal rats,but it was not found in fetal rats.In conclusion,vasa gene plays an important role in the development of germ cells.However,as a marker,it can only be used to label all kinds of germ cells after formation of prespermatogonia.
Journal Article
The Characteristics of vasa Gene from Japanese Sea Bass (Lateolabraxjaponicas) and Its Response to the External Hormones
2015
The RNA helicase Vasa is an important regulator of primordial germ cell development. Its function in mature fish, espe- cially the hormone-related differences in maturing male fish has seldom been documented. In this study, a full length cDNA sequence of the vasa gene was cloned from Japanese sea bass, Lateolabraxjaponicas, and it was namedjsb-vasa. Homology analysis showed thatjsb-vasa was closely related to its teleost homologs. The spatial distribution ofjsb-vasa indicated that it was only highly ex- pressed in testis, showing its germ cell-specific expression pattern. During the testicular development cycle, jsb-vasa was highly expressed during early period of spermatogenesis, and reduced when spermatogenesis advanced. In addition, the jsb-vasa gene ex- pression was significantly inhibited at 6 h, 12 h and 24 h after injecting hCG (human ehorionic gonadotropin) and GnRHa (Gonad- otropin-releasing hormone analogue), indicating thatjsb-vasa gene may play an important role in spermatogenesis of Japanese sea bass, and be under the regulation of external sex hormones.
Journal Article
Derivation of male germ cells from induced pluripotent stem (iPS) cells: a novel and crucial source for generating male gametes
One of the most significant findings in recent stem cell research is the establishment of the induced pluripotent stem (iPS) cells, because they could have critical implications in both regenerative and repro- ductive medicine. Male gametes play a crucial role in transmitting genetic information to subsequent generations, and notably there are more and more patients with azoospermia, due to genetic and environmental factors. Recent advancements on generation of male gametes from human iPS cells would bring great promise to produce patient own male gametes for treating male infertility and provide an excellent platform for unveiling molecular mechanisms of male germ cell development.
Journal Article
Histological Observation of Germ Cell Development and Discovery of Spermatophores in Ovoviviparous Black Rockfish(Sebastes schlegeli Hilgendorf) in Reproductive Season
Black rockfish(Sebastes schlegeli) is an important species for culture; however, its reproductive characteristics have not been fully documented. In this study, we investigated the morphology and developmental process of germ cells in this ovoviviparous rockfish in reproductive season(October 2011–November 2012) with histological methods. We found that the gonad of mature fish showed notable seasonal changes in developmental characteristics and morphological structure. The sperm cells matured during a period lasting from October to December, significantly earlier than the oocytes did. A large number of spermatozoa and other cells occurred in testis at different developmental stages. Vitellogenesis in oocytes began in October, and gestation appeared in April next year. Spermatophores were discovered for the first time in Sebastes, which assembled in testis, main sperm duct, oviduct and genital tract, as well as ovarian cavity in October and April. These organs may serve either as production or hiding places for spermatophores and spermatozoa which were stored and transported in form of spermatophores. Testicular degeneration started from the distal part of testis in April, with spermatophores assembled in degenerating testis and waiting for transportation. The copulation probably lasted for a long period, during which the spermatozoa were discharged in batches as spermatophores. These spermatophores were coated with sticky materials secreted from the interstitial areas of testis and the main sperm duct, then transported into ovary.
Journal Article