
浏览全部资源
扫码关注微信
收稿:2018-01-25,
纸质出版:2018-08-30
移动端阅览
肖诗维, 郝杰, 李冲, 等.
Shiwei XIAO, Jie HAO, Chong LI, et al.
肖诗维, 郝杰, 李冲, 等.
Shiwei XIAO, Jie HAO, Chong LI, et al.
Objective
2
To investigate the potential role of leucine-rich-alpha-2-glycoprotein 1 (
Lrg1
) in the biological functions of the testis by
Lrg1
deficiency mice.
Methods
2
Lrg1
knock-out mice were generated using Crispr/cas9 technology.Six 4-month-old
Lrg1
knock-out mice and 6 wild type mice served as experimental group and control group
respectively.Then
testicular damage was evaluated by HE staining.Serum levels of luteinizing hormone (LH) and testosterone
and intratesticular testosterone level from testis homogenates were measured with ELISA.High throughput Global gene expression analysis was performed for transcriptional levels of the genes in the testis.
Results
2
LRG1 was expressed in the spermatogonial cells and spermatocytes.Western blotting and immunofluorescence assay showed that the expr
ession of
Lrg1
was absent in the testis of
Lrg1
knock-out mice.The knock-out of
Lrg1
resulted in the development of testis
including decreased diameter of seminiferous tubules (196.22±27.88
vs
183.67±26.32 μm
P
<
0.05)
increased degenerated germ cells (26.17±5.03
vs
196.00±40.34
P
<
0.01)
reduced average number of round spermatids per seminiferous tubule (76.00±12.45
vs
60.00±11.40 cells/tubule
P
<
0.01)
lowered serum testosterone level (2.90±0.92
vs
1.90±0.29 ng/mL
P
<
0.05)
and decreased amount and vitality of spermatozoa in the epididymis.Bioinformatics analysis revealed that the altered gene expression induced by
Lrg1
deficiency mainly involved in meiosis
mitosis
chromosome segregation
spermatogenesis
and metabolism processes.In addition
48 members of the C2H2-type zinc finger protein family and 17 miRNAs were identified as deregulated in
Lrg1
-deficient testis
indicating that the testicular transcriptional regulatory network was altered.
Conclusion
2
Lrg1
takes part in spermatogenesis and steroidogenesis in the testis.
INHORN M C PATRIZIO P Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century Hum Reprod Update 2015 21 4 411 426 10.1093/humupd/dmv016 INHORN M C, PATRIZIO P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century[J]. Hum Reprod Update, 2015, 21(4):411-426. DOI:10.1093/humupd/dmv016.
FURUKAWA K KAWAMOTO K EGUCHI H Clinicopathological significance of leucine-rich alpha2-glycoprotein-1 in sera of patients with pancreatic cancer Pancreas 2015 44 1 93 98 10.1097/MPA.0000000000000205 FURUKAWA K, KAWAMOTO K, EGUCHI H, et al . Clinicopathological significance of leucine-rich alpha2-glycoprotein-1 in sera of patients with pancreatic cancer[J ] . Pancreas, 2015, 44(1):93-98.DOI: 10.1097/MPA.0000000000 000205.
ZHANG H CAO J LI L Identification of urine protein biomarkers with the potential for early detection of lung cancer Sci Rep 2015 5 11805 10.1038/srep11805 ZHANG H, CAO J, LI L, et al . Identification of urine protein biomarkers with the potential for early detection of lung cancer[J ] . Sci Rep, 2015, 5:11805. DOI:10.1038/srep11805.
PEKS L TAVINTHARAN S WANG X Elevation of a novel angiogenic factor, leucine-rich-alpha2-glycoprotein (LRG1), is associated with arterial stiffness, endothelial dysfunction, and peripheral arterial disease in patients with type 2 diabetes J Clin Endocrinol Metab 2015 100 4 1586 1593 10.1210/jc.2014-3855 PEKS L, TAVINTHARAN S, WANG X, et al . Elevation of a novel angiogenic factor, leucine-rich-alpha2-glycoprotein (LRG1), is associated with arterial stiffness, endothelial dysfunction, and peripheral arterial disease in patients with type 2 diabetes[J ] . J Clin Endocrinol Metab, 2015, 100(4):1586-1593.DOI: 10.1210/jc.2014-3855.
WANG X ABRAHAM S MCKENZIE J A G LRG1 promotes angiogenesis by modulating endothelial TGF-beta signalling Nature 2013 499 7458 306 311 10.1038/nature12345 WANG X, ABRAHAM S, MCKENZIE J A G, et al . LRG1 promotes angiogenesis by modulating endothelial TGF-beta signalling[J ] . Nature, 2013, 499(7458):306-311. DOI:10.1038/nature12345.
MATZUK M M MCKEOWN M R FILIPPAKOPOULOS P Small-molecule inhibition of BRDT for male contraception Cell 2012 150 4 673 684 10.1016/j.cell.2012.06.045 MATZUK M M, MCKEOWN M R, FILIPPAKOPOULOS P, et al . Small-molecule inhibition of BRDT for male contraception[J ] . Cell, 2012, 150(4):673-684. DOI:10.1016/j.cell.2012.06.045.
LI B DEWEY C N RSEM:accurate transcript quantification from RNA-Seq data with or without a reference genome BMC Bioinformatics 2011 12 323 10.1186/1471-2105-12-323 LI B, DEWEY C N. RSEM:accurate transcript quantification from RNA-Seq data with or without a reference genome[J]. BMC Bioinformatics, 2011, 12:323. DOI:10.1186/1471-2105-12-323.
TARAZONA S GARCIA-ALCALDE F DOPAZO J Differential expression in RNA-seq:a matter of depth Genome Res 2011 21 12 2213 2223 10.1101/gr.124321.111 TARAZONA S, GARCIA-ALCALDE F, DOPAZO J, et al . Differential expression in RNA-seq:a matter of depth[J ] . Genome Res, 2011, 21(12):2213-2223. DOI:10.1101/gr.124321.111.
TAKEMOTO N SERADA S FUJIMOTO M Leucine-rich alpha-2-glycoprotein promotes TGFbeta1-mediated growth suppression in the Lewis lung carcinoma cell lines Oncotarget 2015 6 13 11009 11022 10.18632/oncotarget.3557 TAK EMOTO N, SERADA S, FUJIMOTO M, et al . Leucine-rich alpha-2-glycoprotein promotes TGFbeta1-mediated growth suppression in the Lewis lung carcinoma cell lines[J ] . Oncotarget, 2015, 6(13):11009-11022. DOI:10.18632/oncotarget.3557.
WANG Y CHEN F YE L Steroidogenesis in Leydig cells: effects of aging and environmental factors Reproduction 2017 154 4 R111 R122 10.1530/REP-17-0064 WANG Y, CHEN F, YE L, et al . Steroidogenesis in Leydig cells: effects of aging and environmental factors[J ] . Reproduction, 2017, 154(4):R111-R122. DOI:10.1530/REP-17-0064.
RAMASWAMY S WEINBAUER G F Endocrine control of spermatogenesis:Role of FSH and LH/testosterone Spermatogenesis 2014 4 2 e996025 10.1080/21565562.2014.996025 RAMASWAMY S, WEINBAUER G F. Endocrine control of spermatogenesis:Role of FSH and LH/testosterone[J]. Spermatogenesis, 2014, 4(2):e996025. DOI: 10.1080/21565562.2014.996025.
LADD J J BUSALD T JOHNSON M M Increased plasma levels of the APC-interacting protein MAPRE1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women Cancer Prev Res (Phila) 2012 5 4 655 664 10.1158/1940-6207.CAPR-11-0412 LADD J J, BUSALD T, JOHNSON M M, et al . Increased plasma levels of the APC-interacting protein MAPRE1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women[J ] . Cancer Prev Res (Phila), 2012, 5(4):655-664. DOI:10.1158/1940-6207.CAPR-11-0412.
PARK E SONG C H PARK J I Transforming growth factor-beta1 signaling represses testicular steroidogenesis through cross-talk with orphan nuclear receptor Nur77 PLoS One 2014 9 8 e104812 10.1371/journal.pone.0104812 PARK E, SONG C H, PARK J I, et al . Transforming growth factor-beta1 signaling represses testicular steroidogenesis through cross-talk with orphan nuclear receptor Nur77[J ] . PLoS One, 2014, 9(8):e104812. DOI:10.1371/journal.pone.0104812.
WOJTASZ L DANIEL K ROIG I Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase PLoS Genet 2009 5 10 e1000702 10.1371/journal.pgen.1000702 WOJTASZ L, DANIEL K, ROIG I, et al . Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase[J ] . PLoS Genet, 2009, 5(10):e1000702. DOI:10.1371/journal.pgen.1000702.
UHLMANN F SMC complexes:from DNA to chromosomes Nat Rev Mol Cell Biol 2016 17 7 399 412 10.1038/nrm.2016.30 UHLMANN F. SMC complexes:from DNA to chromosomes[J]. Nat Rev Mol Cell Biol, 2016, 17(7):399-412. DOI:10.1038/nrm.2016.30.
ALVAREZ-FERNANDEZ M SANCHEZ-MARTINEZ R SANZ-CASTILLO B Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals Proc Natl Acad Sci U S A 2013 110 43 17374 17379 10.1073/pnas.1310745110 ALVAREZ-FERNANDEZ M, SANCHEZ-MARTINEZ R, SANZ-CASTILLO B, et al . Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals[J ] . Proc Natl Acad Sci U S A, 2013, 110(43):17374-17379. DOI:10.1073/pnas.1310745110.
SEO E K CHOI J Y JEONG J H Crystal structure of C-terminal coiled-coil domain of SYCP1 reveals non-canonical anti-parallel dimeric structure of transverse filament at the synaptonemal complex PLoS One 2016 11 8 e0161379 10.1371/journal.pone.0161379 SEO E K, CHOI J Y, JEONG J H, et al . Crystal structure of C-terminal coiled-coil domain of SYCP1 reveals non-canonical anti-parallel dimeric structure of transverse filament at the synaptonemal complex[J ] . PLoS One, 2016, 11(8):e0161379. DOI:10.1371/journal.pone.0161379.
RATO L MENESES M J SILVA B M New insights on hormones and factors that modulate Sertoli cell metabolism Histol Histopathol 2016 31 5 499 513 10.14670/HH-11-717 RATO L, MENESES M J, SILVA B M, et al . New insights on hormones and factors that modulate Sertoli cell metabolism[J ] . Histol Histopathol, 2016, 31(5):499-513. DOI:10.14670/HH-11-717.
RATO L ALVES M G SOCORRO S Metabolic regulation is important for spermatogenesis Nat Rev Urol 2012 9 6 330 338 10.1038/nrurol.2012.77 RATO L, ALVES M G, SOCORRO S, et al . Metabolic regulation is important for spermatogenesis[J ] . Nat Rev Urol, 2012, 9(6):330-338. DOI:10.1038/nrurol.2012.77.
AGUDA B D Modeling microRNA-transcription factor networks in cancer Adv Exp Med Biol 2013 774 149 167 10.1007/978-94-007-5590-1_9 AGUDA B D. Modeling microRNA-transcription factor networks in cancer[J]. Adv Exp Med Biol, 2013, 774:149-167. DOI:10.1007/978-94-007-5590-1_9.
ARDA H E WALHOUT A J Gene-centered regulatory networks Brief Funct Genomics 2010 9 1 4 12 10.1093/bfgp/elp049 ARDA H E, WALHOUT A J. Gene-centered regulatory networks[J]. Brief Funct Genomics, 2010, 9(1):4-12. DOI:10.1093/bfgp/elp049.
JIN S CHOI H KWON J T Identification of target genes for spermatogenic cell-specific KRAB transcription factor ZFP819 in a male germ cell line Cell Biosci 2017 7 4 10.1186/s13578-016-0132-4 JIN S, CHOI H, KWON J T, et al . Identification of target genes for spermatogenic cell-specific KRAB transcription factor ZFP819 in a male germ cell line[J ] . Cell Biosci, 2017, 7:4. DOI:10.1186/s13578-016-0132-4.
JIN S CHOI H KWON J T Identification and characterization of reproductive KRAB-ZF genes in mice Gene 2015 565 1 45 55 10.1016/j.gene.2015.03.059 JIN S, CHOI H, KWON J T, et al . Identification and characterization of reproductive KRAB-ZF genes in mice[J ] . Gene, 2015, 565(1):45-55. DOI:10.1016/j.gene.2015.03.059.
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621