Five azacytidine, a DNA methyltransferase inhibitor, specifically inhibits testicular cord formation and Sertoli cell differentiation in vitro.

Abstract:

:In mammals, Sry, Sox9, and M33 act as regulators at a chromatin level and promote the maturation of embryonic gonads into testes. Recently, it was shown that transcriptional regulation by DNA methylation plays crucial roles in gene expression during the differentiation and development of various cell types. To determine the involvement of DNA methylation in sex determination of the gonad, we developed and performed organ culture of gonad with the DNA methyltransferase inhibitor 5-azacytidine to induce global DNA methylation status changes. In vitro treatment with 5-azacytidine specifically inhibited testicular cord formation in a dose-dependent manner; however, no appreciable defect was observed in ovarian explants. Inhibition of testicular cord was observed only in gonads from 11.5 days post-coitus embryos. These effects were not observed in 5-azacytidine-treated gonads from 12.0 days post-coitus embryos. To determine the effect of 5-azacytidine on Sertoli and Leydig cell differentiation in the testis, we performed whole mount in situ hybridization analysis. The Leydig and stromal cell marker genes Lhx9, Mfge8, and 3beta-Hsd were normally induced in 5-azaytidine-treated testicular explants. Sertoli cell marker genes, Sox9 and MIS were normally induced, but Col9a3, encoding an extracellular matrix component, was inhibited in 5-azacytidine-treated testicular explants. Thus, our data show that DNA methylation is involved in testicular cord formation and Sertoli cell differentiation, acting directly on the gonad at 11.5 days post-coitus.

journal_name

Mol Reprod Dev

authors

Mizukami T,Kanai Y,Fujisawa M,Kanai-Azuma M,Kurohmaru M,Hayashi Y

doi

10.1002/mrd.20850

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

1002-10

issue

6

eissn

1040-452X

issn

1098-2795

journal_volume

75

pub_type

杂志文章
  • Characterization of a novel, testis-specific equine serine/threonine kinase.

    abstract::Testis-specific protein kinases are important because of their potential role in spermiogenesis, sperm maturation, and sperm function. In the present study, a novel serine-threonine kinase with high identity to human serine-threonine kinase 31 (STK31) was cloned from equine testis and expression of the protein was cha...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20792

    authors: Sabeur K,Ball BA,Corbin CJ,Conley A

    更新日期:2008-05-01 00:00:00

  • Genetic modification of primordial germ cells by gene trapping, gene targeting, and phiC31 integrase.

    abstract::The genome of germline committed cells is thought to be protected by mechanisms of transcriptional silencing, posing a barrier to transgenesis using cultured germline cells. We found that selection for transgene integration into the primordial germ cell genome required that the transgenes be flanked by the chicken bet...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20859

    authors: Leighton PA,van de Lavoir MC,Diamond JH,Xia C,Etches RJ

    更新日期:2008-07-01 00:00:00

  • Increased expression of NADH-ubiquinone oxidoreductase chain 2 (ND2) in preimplantation rabbit embryos cultured with 20% oxygen concentration.

    abstract::In vitro culture of mammalian preimplantation embryos is associated with various developmental disorders such as retardation in development and cell damage. The molecular mechanisms underlying these processes are poorly understood. One of the possible reasons may be the unphysiologically high oxygen concentration used...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2795(199804)49:4<394::AID-MRD6>

    authors: Koerber S,Santos AN,Tetens F,Küchenhoff A,Fischer B

    更新日期:1998-04-01 00:00:00

  • Suppression of connexin 43 and E-cadherin transcripts in in vitro derived bovine embryos following culture in vitro or in vivo in the homologous bovine oviduct.

    abstract::In this study, a combination of RNAi and endoscopic transfer to the oviduct of synchronized heifers has been used to investigate the effect of suppression of Cx43 and E-cadherin on the development, mRNA and protein expression of bovine blastocysts cultured in vitro or in vivo. In vitro matured and fertilized bovine zy...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20678

    authors: Tesfaye D,Lonergan P,Hoelker M,Rings F,Nganvongpanit K,Havlicek V,Besenfelder U,Jennen D,Tholen E,Schellander K

    更新日期:2007-08-01 00:00:00

  • Efficient production of intersubspecific hybrid mice and embryonic stem cells by intracytoplasmic sperm injection.

    abstract::Recently, mice and embryonic stem (ES) cells with allelic polymorphisms have been used extensively in the field of genetics and developmental biology. In this study, we examined whether intersubspecific hybrid mice and ES cells with these genotypes can be efficiently produced by intracytoplasmic sperm injection (ICSI)...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20612

    authors: Shinmen A,Honda A,Ohkawa M,Hirose M,Ogonuki N,Yuzuriha M,Miki H,Mochida K,Inoue K,Abe K,Ito M,Ogura A

    更新日期:2007-09-01 00:00:00

  • Fyn kinase activity is required for normal organization and functional polarity of the mouse oocyte cortex.

    abstract::The objective of the present study was to determine whether Fyn kinase participated in signaling events during sperm-egg interactions, sperm incorporation, and meiosis II. The functional requirement of Fyn kinase activity in these events was tested through the use of the protein kinase inhibitor SKI-606 (Bosutinib) an...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.21034

    authors: Luo J,McGinnis LK,Kinsey WH

    更新日期:2009-09-01 00:00:00

  • Cumulus expansion during in vitro maturation of bovine oocytes: relationship with intracellular glutathione level and its role on subsequent embryo development.

    abstract::Glutamine (GLN) is a metabolic precursor for hexosamine synthesis and its inclusion in culture medium has been reported to improve cumulus expansion. Glutamine and cysteine share the same transport system. Excess external GLN may act as a competitive inhibitor for the uptake of cysteine and stimulate loss of cellular ...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2795(199809)51:1<76::AID-MRD9>3

    authors: Furnus CC,de Matos DG,Moses DF

    更新日期:1998-09-01 00:00:00

  • Requirements of Src family kinase during meiotic maturation in mouse oocyte.

    abstract::The Src family kinase (SFK) is important in normal cell cycle control. However, its role in meiotic maturation in mammalian has not been examined. We used confocal microscope immunofluorescence to examine the in vitro dynamics of the subcellular distribution of SFK during the mouse oocyte meiotic maturation and furthe...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20613

    authors: Zheng KG,Meng XQ,Yang Y,Yu YS,Liu DC,Li YL

    更新日期:2007-01-01 00:00:00

  • Glycogen synthase kinase-3 regulation of chromatin segregation and cytokinesis in mouse preimplantation embryos.

    abstract::Glycogen synthase kinase-3 (GSK-3) is a highly conserved serine/threonine protein kinase implicated in diverse cellular processes. Activity of GSK-3 is essential for meiotic chromatin segregation in oocytes, yet expression and/or function of GSK-3 have not been reported in mammalian preimplantation embryos. Objectives...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20495

    authors: Acevedo N,Wang X,Dunn RL,Smith GD

    更新日期:2007-02-01 00:00:00

  • Role of forward-motility-stimulating factor as an extracellular activator of soluble adenylyl cyclase.

    abstract::Forward-motility-stimulating factor (FMSF) is a protein, originally purified from bubaline serum, that promotes progressive motility of mature spermatozoa. FMSF binds to sperm surface receptors and activates transmembrane adenylyl cyclase (tmAC), causing a rise in intracellular cyclic AMP level ([cAMP]i) and subsequen...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.22586

    authors: Dey S,Roy D,Majumder GC,Mukherjee B,Bhattacharyya D

    更新日期:2015-12-01 00:00:00

  • Activated bovine cytoplasts prepared by demecolcine-induced enucleation support development of nuclear transfer embryos in vitro.

    abstract::Demecolcine-induced enucleation (IE) of mouse oocytes has been shown to improve development to term of cloned mice. In this study, we characterized the kinetics and morphological progression of bovine oocytes subjected to IE, and evaluated their ability to support embryo development to the blastocyst stage after nucle...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20356

    authors: Russell DF,Ibáñez E,Albertini DF,Overström EW

    更新日期:2005-10-01 00:00:00

  • Sry and Sox9 expression during canine gonadal sex determination assayed by quantitative reverse transcription-polymerase chain reaction.

    abstract::Testis induction is associated with gonadal Sry and Sox9 expression in mammals, and with Sox9 expression in vertebrates where Sry is absent. In mammals, Sry might initiate testis induction by upregulating Sox9 expression; however, direct evidence supporting this hypothesis is lacking. Models of Sry-negative XX sex rev...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.10317

    authors: Meyers-Wallen VN

    更新日期:2003-08-01 00:00:00

  • Embryo development, oocyte morphology, and kinetics of meiotic maturation in bovine oocytes exposed to 6-dimethylaminopurine prior to in vitro maturation.

    abstract::The developmental competence of bovine follicular oocytes that had been meiotically arrested with the phosphokinase inhibitor 6-dimethylaminopurine (6-DMAP) was studied. After 24 h in vitro culture with 2 mM 6-DMAP, 85 +/- 12% of the oocytes were at the germinal vesicle stage compared to 97 +/- 3% at the start of cult...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2795(199807)50:3<334::AID-MRD10

    authors: Avery B,Hay-Schmidt A,Hyttel P,Greve T

    更新日期:1998-07-01 00:00:00

  • Expression of a plasmin/trypsin Kunitz inhibitor by pig trophoblast.

    abstract::Under the influence of progesterone, the porcine uterus synthesizes plasmin/trypsin inhibitor (PTI), a low molecular weight protein (M(r) approximately 14,000) belonging to the Kunitz family of proteinase inhibitors. Here it is demonstrated that mRNA for the same protein is produced by the developing trophoblast durin...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2795(199704)46:4<443::AID-MRD1>

    authors: Duffy JY,Stallings-Mann ML,Trout WE,Roberts RM

    更新日期:1997-04-01 00:00:00

  • Differential expression of genes for transcription factors in theca and granulosa cells following selection of a dominant follicle in cattle.

    abstract::Transcription factors inhibit or assist RNA polymerases in the initiation and maintenance of transcription; however, the cell specific expression and roles of transcription factors within bovine ovarian follicles during development are unknown. The aim of present study was to determine if the expression of transcripti...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20819

    authors: Zielak AE,Canty MJ,Forde N,Coussens PM,Smith GW,Lonergan P,Ireland JJ,Evans AC

    更新日期:2008-05-01 00:00:00

  • Effect of vitrification on mitochondrial distribution and membrane potential in mouse two pronuclear (2-PN) embryos.

    abstract::The present study was designed to investigate the effect of vitrification on mitochondrial distribution, membrane potential (Deltapsi) and microtubule distribution in mouse 2-PN embryos, as well as to document the relationship between mitochondrial distribution and developmental ability of those embryos. Mitochondrial...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.21064

    authors: Zhao XM,Fu XW,Hou YP,Yan CL,Suo L,Wang YP,Zhu HB,Dinnyés A,Zhu SE

    更新日期:2009-11-01 00:00:00

  • Effects of hyperstimulation with gonadotrophins and age of females on oocytes and their metaphase II status in rats.

    abstract::The present study was undertaken to evaluate the effects of hyperstimulation and aging on the number and proportion of oocytes in the metaphase II stage in female Wistar rats. It explored the validity of the hypothesis that a combination of hyperstimulation with pregnant mare serum gonadotrophins (PMSG) and age could ...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2795(200001)55:1<104::AID-MRD14

    authors: Tain CF,Goh VH,Ng SC

    更新日期:2000-01-01 00:00:00

  • Protein kinase C activity in mouse eggs regulates gamete membrane interaction.

    abstract::Gamete membrane interaction is critical to initiate the development of a new organism. The signaling pathways governing this event, however, are poorly understood. In this report, we provide the first evidence that protein kinase C activity in mouse eggs plays a crucial role in the regulation of this process. Stimulat...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20718

    authors: Akabane H,Fan J,Zheng X,Zhu GZ

    更新日期:2007-11-01 00:00:00

  • Lipopolysaccharide-induced expression of FAS ligand in cultured immature boar sertoli cells through the regulation of pro-inflammatory cytokines and miR-187.

    abstract::Lipopolysaccharide (LPS) induces germ cell apoptosis, but its mechanism of action is not clear. One possibility is that LPS regulates the expression of FAS ligand (FASLG) in Sertoli cells, which will then influence germ cell apoptosis. In this study, LPS reduced the viability of cultured, immature boar Sertoli cells i...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.22534

    authors: Wang Y,Zhang JJ,Yang WR,Luo HY,Zhang JH,Wang XZ

    更新日期:2015-11-01 00:00:00

  • Follicle-oocyte atresia and temporal taphonomy in cold-stored domestic cat ovaries.

    abstract::In vitro oocyte maturation followed by in vitro fertilization (IVM/IVF) success in the domestic cat remains inferior to commonly studied livestock or laboratory species. The objectives here were (1) to histologically assess atresia status of freshly excised follicle/oocyte complexes, and (2) to evaluate taphonomic cha...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2795(199702)46:2<190::AID-MRD9>

    authors: Wood TC,Montali RJ,Wildt DE

    更新日期:1997-02-01 00:00:00

  • Annexin A2 is involved in pig (Sus scrofa)sperm-oviduct interaction.

    abstract::The oviduct is a dynamic organ which modulates gamete physiology. Sperm-oviduct interaction provides the formation of a sperm storage reservoir and allows the selection of sperm with certain qualities in eutherian mammals. In sows, the oviductal sperm binding glycoprotein (SBG) has been proposed to be involved in sper...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20958

    authors: Teijeiro JM,Ignotz GG,Marini PE

    更新日期:2009-04-01 00:00:00

  • Identification of the cadherin subtypes present in the human peritoneum and endometriotic lesions: potential role for P-cadherin in the development of endometriosis.

    abstract::Endometriosis is defined as endometrial tissue outside of the uterine cavity. The pathogenesis of this common disease remains poorly understood. However, the implantation and invasion of the viable cells from retrograde menstruation into the peritoneum is a widely accepted theory. To date, the mechanisms by which cell...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.10121

    authors: Chen GT,Tai CT,Yeh LS,Yang TC,Tsai HD

    更新日期:2002-07-01 00:00:00

  • Effects of differentiation on the transcriptional regulation of the FGF-4 gene: critical roles played by a distal enhancer.

    abstract::Embryonal carcinoma (EC) cells are used widely as a model system for studying the expression of developmentally regulated genes, in particular genes that are regulated at the transcriptional level when EC cells differentiate. This review focuses on the molecular mechanisms that govern the transcription of the fibrobla...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章,评审

    doi:10.1002/(SICI)1098-2795(199810)51:2<218::AID-MRD12

    authors: Lamb KA,Rizzino A

    更新日期:1998-10-01 00:00:00

  • Localization of microfilaments and a tubulin-like protein in crustacean (Rhynchocinetes typus) spermatozoon.

    abstract::Sperm from the decapod crustacean Rhynchocinetes typus undergo dramatic shape changes as they pass from the vas deferens to seawater and interact with the oocyte envelopes. Using FITC-phalloidin and antitubulin antibodies, we were able to localize microfilaments and a tubulin-like protein in R. typus spermatozoon. Mic...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.1080280410

    authors: Perez C,Roco M,Castro A,Dupre E,Schatten G,Barros C

    更新日期:1991-04-01 00:00:00

  • Coactivator CBP in the regulation of conceptus IFNtau gene transcription.

    abstract::Studies of ovine interferon-tau (oIFNtau) gene regulation, an anti-luteolytic factor produced by conceptuses of the ruminant ungulates, have been carried out, but a definitive mechanism for its spatial-temporal transcription has not been elucidated. Recently, specific binding regions for transcription factors AP-1 and...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.10293

    authors: Xu N,Takahashi Y,Matsuda F,Sakai S,Christenson RK,Imakawa K

    更新日期:2003-05-01 00:00:00

  • Chimeric honeybees (Apis mellifera) produced by transplantation of embryonic cells into pre-gastrula stage embryos and detection of chimerism by use of microsatellite markers.

    abstract::The production of chimeras, by use of cell transplantation, has proved to be highly valuable in studies of development by providing insights into cell fate, differentiation, and developmental potential. So far, chimeric honeybees have been created by nuclear transfer technologies. We have developed protocols to produc...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.20435

    authors: Bergem M,Norberg K,Roseth A,Meuwissen T,Lien S,Aamodt RH

    更新日期:2006-04-01 00:00:00

  • Evolution of octopod sperm I: comparison of nuclear morphogenesis in Eledone and Octopus.

    abstract::Morphogenesis of the Eledone cirrhosa sperm nucleus, as studied by electron microscopic techniques, is compared with that of Octopus vulgaris. Both species of cephalopods belong to the family Octopodidae. The results indicate that extensive nuclear helicoidization during E. cirrhosa spermiogenesis is brought about by ...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.10124

    authors: Gimenez-Bonafé P,Ribes E,Zamora MJ,Kasinsky HE,Chiva M

    更新日期:2002-07-01 00:00:00

  • Fibrinogen-related protein, FGL2, of hamster cauda epididymal fluid: Purification, kinetic analysis of its prothrombinase activity, and its role in segregation of nonviable spermatozoa.

    abstract::Although the epididymal environment promotes the maturation and survival of spermatozoa, not all spermatozoa remain viable during passage through the epididymis. Does the epididymis has a protective mechanism(s) to segregate the viable sperm from defective spermatozoa? Previously, we identified 260/280 kDa oligomers (...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.23438

    authors: Nagdas SK,Wallace S,Eaford D,Baker R,Carr K,Raychoudhuri SS

    更新日期:2020-12-01 00:00:00

  • Alterations and reversibility in the chromatin, cytoskeleton and development of pig oocytes treated with roscovitine.

    abstract::Germinal vesicle (GV) breakdown in mammalian oocytes is regulated by the activation of maturation promoting factor (MPF). We investigated a specific cdc2 kinase inhibitor, roscovitine, to maintain pig oocytes in the GV stage. Cumulus-oocyte complexes (COCs) were aspirated from slaughterhouse ovaries and cultured for 4...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.10234

    authors: Ju JC,Tsay C,Ruan CW

    更新日期:2003-04-01 00:00:00

  • Synthesis and developmental regulation of an egg specific mouse protein translated from maternal mRNA.

    abstract::Proteins synthesized by DDK mice embryos were analyzed by 2D electrophoresis and a new egg-specific polypeptide, D14, was identified. The protein is characterized by its high rate of synthesis and electrophoretic properties (MW 36,500, pl greater than 8). The synthesis of D14 is strictly developmentally regulated: sta...

    journal_title:Molecular reproduction and development

    pub_type: 杂志文章

    doi:10.1002/mrd.1080280303

    authors: Richoux V,Renard JP,Babinet C

    更新日期:1991-03-01 00:00:00