Analysis of the equine "cumulome" reveals major metabolic aberrations after maturation in vitro.
Coagulation
Complement
Cumulus
Glucose
IVM
Metabolomics
Oocyte
Oxygen
Proteomics
Purine
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
17 Jul 2019
17 Jul 2019
Historique:
received:
02
10
2018
accepted:
23
05
2019
entrez:
19
7
2019
pubmed:
19
7
2019
medline:
18
12
2019
Statut:
epublish
Résumé
Maturation of oocytes under in vitro conditions (IVM) results in impaired developmental competence compared to oocytes matured in vivo. As oocytes are closely coupled to their cumulus complex, elucidating aberrations in cumulus metabolism in vitro is important to bridge the gap towards more physiological maturation conditions. The aim of this study was to analyze the equine "cumulome" in a novel combination of proteomic (nano-HPLC MS/MS) and metabolomic (UPLC-nanoESI-MS) profiling of single cumulus complexes of metaphase II oocytes matured either in vivo (n = 8) or in vitro (n = 7). A total of 1811 quantifiable proteins and 906 metabolic compounds were identified. The proteome contained 216 differentially expressed proteins (p ≤ 0.05; FC ≥ 2; 95 decreased and 121 increased in vitro), and the metabolome contained 108 metabolites with significantly different abundance (p ≤ 0.05; FC ≥ 2; 24 decreased and 84 increased in vitro). The in vitro "cumulome" was summarized in the following 10 metabolic groups (containing 78 proteins and 21 metabolites): (1) oxygen supply, (2) glucose metabolism, (3) fatty acid metabolism, (4) oxidative phosphorylation, (5) amino acid metabolism, (6) purine and pyrimidine metabolism, (7) steroid metabolism, (8) extracellular matrix, (9) complement cascade and (10) coagulation cascade. The KEGG pathway "complement and coagulation cascades" (ID4610; n = 21) was significantly overrepresented after in vitro maturation. The findings indicate that the in vitro condition especially affects central metabolism and extracellular matrix composition. Important candidates for the metabolic group oxygen supply were underrepresented after maturation in vitro. Additionally, a shift towards glycolysis was detected in glucose metabolism. Therefore, under in vitro conditions, cumulus cells seem to preferentially consume excess available glucose to meet their energy requirements. Proteins involved in biosynthetic processes for fatty acids, cholesterol, amino acids, and purines exhibited higher abundances after maturation in vitro. This study revealed the marked impact of maturation conditions on the "cumulome" of individual cumulus oocyte complexes. Under the studied in vitro milieu, cumulus cells seem to compensate for a lack of important substrates by shifting to aerobic glycolysis. These findings will help to adapt culture media towards more physiological conditions for oocyte maturation.
Sections du résumé
BACKGROUND
BACKGROUND
Maturation of oocytes under in vitro conditions (IVM) results in impaired developmental competence compared to oocytes matured in vivo. As oocytes are closely coupled to their cumulus complex, elucidating aberrations in cumulus metabolism in vitro is important to bridge the gap towards more physiological maturation conditions. The aim of this study was to analyze the equine "cumulome" in a novel combination of proteomic (nano-HPLC MS/MS) and metabolomic (UPLC-nanoESI-MS) profiling of single cumulus complexes of metaphase II oocytes matured either in vivo (n = 8) or in vitro (n = 7).
RESULTS
RESULTS
A total of 1811 quantifiable proteins and 906 metabolic compounds were identified. The proteome contained 216 differentially expressed proteins (p ≤ 0.05; FC ≥ 2; 95 decreased and 121 increased in vitro), and the metabolome contained 108 metabolites with significantly different abundance (p ≤ 0.05; FC ≥ 2; 24 decreased and 84 increased in vitro). The in vitro "cumulome" was summarized in the following 10 metabolic groups (containing 78 proteins and 21 metabolites): (1) oxygen supply, (2) glucose metabolism, (3) fatty acid metabolism, (4) oxidative phosphorylation, (5) amino acid metabolism, (6) purine and pyrimidine metabolism, (7) steroid metabolism, (8) extracellular matrix, (9) complement cascade and (10) coagulation cascade. The KEGG pathway "complement and coagulation cascades" (ID4610; n = 21) was significantly overrepresented after in vitro maturation. The findings indicate that the in vitro condition especially affects central metabolism and extracellular matrix composition. Important candidates for the metabolic group oxygen supply were underrepresented after maturation in vitro. Additionally, a shift towards glycolysis was detected in glucose metabolism. Therefore, under in vitro conditions, cumulus cells seem to preferentially consume excess available glucose to meet their energy requirements. Proteins involved in biosynthetic processes for fatty acids, cholesterol, amino acids, and purines exhibited higher abundances after maturation in vitro.
CONCLUSION
CONCLUSIONS
This study revealed the marked impact of maturation conditions on the "cumulome" of individual cumulus oocyte complexes. Under the studied in vitro milieu, cumulus cells seem to compensate for a lack of important substrates by shifting to aerobic glycolysis. These findings will help to adapt culture media towards more physiological conditions for oocyte maturation.
Identifiants
pubmed: 31315563
doi: 10.1186/s12864-019-5836-5
pii: 10.1186/s12864-019-5836-5
pmc: PMC6637639
doi:
Substances chimiques
Proteome
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
588Subventions
Organisme : Universität Zürich
ID : Grant FK-13-062
Références
Biol Reprod. 2000 Mar;62(3):579-88
pubmed: 10684798
Theriogenology. 2001 Feb 1;55(3):705-15
pubmed: 11245260
Glycobiology. 2001 Mar;11(3):183-94
pubmed: 11320057
J Cell Biochem Suppl. 2001;Suppl 36:232-46
pubmed: 11455588
Reproduction. 2001 Oct;122(4):619-28
pubmed: 11570969
Cell Struct Funct. 2001 Aug;26(4):189-96
pubmed: 11699635
Anim Reprod Sci. 2002 Feb 15;69(3-4):175-86
pubmed: 11812628
Biol Reprod. 2002 Jul;67(1):256-62
pubmed: 12080025
Equine Vet J. 2002 Jul;34(4):378-82
pubmed: 12117110
Obstet Gynecol. 2002 Oct;100(4):665-70
pubmed: 12383531
Biol Reprod. 2003 Jan;68(1):1-9
pubmed: 12493688
Biol Reprod. 2003 Sep;69(3):1013-22
pubmed: 12773434
Reprod Biol Endocrinol. 2003 May 28;1:45
pubmed: 12809557
J Assist Reprod Genet. 1992 Jun;9(3):211-6
pubmed: 1381974
Fertil Steril. 1992 Nov;58(5):964-9
pubmed: 1426383
Anal Chem. 2003 Sep 1;75(17):4646-58
pubmed: 14632076
Reprod Domest Anim. 2004 Apr;39(2):70-5
pubmed: 15065986
Reprod Biol Endocrinol. 2004 Jun 22;2:44
pubmed: 15212696
Mol Reprod Dev. 2004 Aug;68(4):492-9
pubmed: 15236335
Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4252-7
pubmed: 15755808
Fertil Steril. 2005 Aug;84(2):464-7
pubmed: 16084891
Ital J Anat Embryol. 2005;110(2 Suppl 1):219-24
pubmed: 16101041
Reproduction. 2005 Oct;130(4):559-67
pubmed: 16183874
J Proteome Res. 2005 Sep-Oct;4(5):1569-74
pubmed: 16212408
Hum Reprod. 2006 Jul;21(7):1705-19
pubmed: 16571642
Mol Endocrinol. 2006 Dec;20(12):3228-39
pubmed: 16931571
Anim Reprod Sci. 2007 Mar;98(1-2):39-55
pubmed: 17101246
Reprod Biomed Online. 2006 Dec;13(6):807-14
pubmed: 17169200
Clin Biochem. 2007 Jun;40(9-10):575-84
pubmed: 17467679
Reproduction. 2007 Jun;133(6):1107-20
pubmed: 17636165
Fertil Steril. 2008 Sep;90(3):546-50
pubmed: 17904128
J Reprod Fertil Suppl. 1991;44:375-84
pubmed: 1795281
Theriogenology. 2008 Jan 1;69(1):23-30
pubmed: 17976712
Development. 2008 Jan;135(1):111-21
pubmed: 18045843
J Proteome Res. 2008 Jan;7(1):29-34
pubmed: 18067246
Reprod Fertil Dev. 2008;20(3):408-17
pubmed: 18402761
Biol Reprod. 2008 Aug;79(2):209-22
pubmed: 18417710
Reproduction. 2008 Aug;136(2):211-24
pubmed: 18456903
Reprod Biomed Online. 2008 Oct;17(4):497-501
pubmed: 18854102
BMC Dev Biol. 2009 Jan 06;9:1
pubmed: 19126199
Proteomics. 2009 Feb;9(3):550-64
pubmed: 19137544
Biol Reprod. 2009 Jul;81(1):199-206
pubmed: 19208544
Nat Methods. 2009 May;6(5):359-62
pubmed: 19377485
Mol Reprod Dev. 2009 Sep;76(9):844-53
pubmed: 19455666
Hum Reprod. 2009 Nov;24(11):2856-67
pubmed: 19625311
Electrophoresis. 2009 Sep;30(17):2967-75
pubmed: 19676090
Mol Reprod Dev. 2010 Jan;77(1):51-8
pubmed: 19728369
J Lipid Res. 2010 May;51(5):1218-27
pubmed: 19965589
J Proteome Res. 2010 Mar 5;9(3):1289-301
pubmed: 20058866
Reproduction. 2010 Apr;139(4):685-95
pubmed: 20089664
Hum Reprod. 2010 May;25(5):1259-70
pubmed: 20228394
Mol Hum Reprod. 2010 Aug;16(8):531-8
pubmed: 20435608
Am J Respir Cell Mol Biol. 2011 Apr;44(4):439-47
pubmed: 20508070
Mol Hum Reprod. 2010 Aug;16(8):513-30
pubmed: 20538894
J Proteomics. 2010 Aug 5;73(9):1740-6
pubmed: 20576481
Mol Reprod Dev. 2010 Aug;77(8):651-61
pubmed: 20652997
Mol Microbiol. 2010 Nov;78(3):545-60
pubmed: 20807208
Reproduction. 2010 Nov;140(5):655-62
pubmed: 20826538
J Assist Reprod Genet. 2011 Feb;28(2):173-88
pubmed: 20953827
Nucleic Acids Res. 2011 Jan;39(Database issue):D52-7
pubmed: 21115458
Reprod Fertil Dev. 2011;23(1):81-93
pubmed: 21366984
Hum Reprod. 2011 May;26(5):1035-51
pubmed: 21372047
Reprod Domest Anim. 2011 Dec;46(6):1017-21
pubmed: 21385232
Dev Biol. 1990 Mar;138(1):16-25
pubmed: 2155145
J Anim Sci. 2011 Nov;89(11):3561-71
pubmed: 21680790
Proteome Sci. 2011 Sep 17;9:54
pubmed: 21923925
PLoS One. 2011;6(11):e27179
pubmed: 22087263
Biol Reprod. 2012 Mar 19;86(3):71
pubmed: 22116803
J Mass Spectrom. 2012 Jan;47(1):29-33
pubmed: 22282086
Arabidopsis Book. 2002;1:e0018
pubmed: 22303196
Endocrinology. 2012 May;153(5):2444-54
pubmed: 22408172
Clin Exp Immunol. 1990 Nov;82(2):359-62
pubmed: 2242616
Biol Reprod. 2012 Aug 30;87(2):46
pubmed: 22649071
Mol Hum Reprod. 2012 Dec;18(12):572-84
pubmed: 22923488
J Obstet Gynaecol Res. 2013 Feb;39(2):522-7
pubmed: 22925265
Reprod Fertil Dev. 2013;25(2):426-38
pubmed: 22950951
Fertil Steril. 2012 Dec;98(6):1574-80.e5
pubmed: 22968048
Reprod Fertil Dev. 2012;25(1):80-93
pubmed: 23244831
Mol Reprod Dev. 2013 Feb;80(2):166-82
pubmed: 23280668
Fertil Steril. 2013 Mar 15;99(4):1073-7
pubmed: 23375196
Fertil Steril. 2013 Mar 1;99(3):663-6
pubmed: 23391409
Int J Dev Biol. 2012;56(10-12):799-808
pubmed: 23417402
PLoS One. 2013 Sep 20;8(9):e74981
pubmed: 24073231
PLoS One. 2013 Oct 16;8(10):e77303
pubmed: 24146976
J Biol Chem. 1986 Apr 15;261(11):4777-80
pubmed: 2420792
Equine Vet J Suppl. 2013 Dec;(45):39-43
pubmed: 24304402
Reprod Fertil Dev. 2015 Jan;27(2):407-18
pubmed: 24388334
Anal Chem. 2014 Apr 15;86(8):3985-93
pubmed: 24640936
Reproduction. 2014 Jul;148(1):R15-27
pubmed: 24760880
Mol Hum Reprod. 2014 Aug;20(8):719-35
pubmed: 24770949
J Biol Chem. 1989 Aug 15;264(23):13840-7
pubmed: 2503506
Int J Mol Sci. 2014 Jul 22;15(7):12972-97
pubmed: 25054321
Mol Endocrinol. 2014 Sep;28(9):1502-21
pubmed: 25058602
Reproduction. 2014 Oct;148(4):429-39
pubmed: 25062802
Biol Reprod. 2014 Nov;91(5):111
pubmed: 25253738
Int J Mol Sci. 2014 Sep 29;15(10):17518-40
pubmed: 25268621
Biomed Res Int. 2014;2014:964614
pubmed: 25276836
Nucleic Acids Res. 2015 Jan;43(Database issue):D447-52
pubmed: 25352553
Hum Reprod. 2015 Jan;30(1):88-96
pubmed: 25355587
Biol Reprod. 2015 Jan;92(1):26
pubmed: 25395682
Int J Inflam. 2014;2014:803237
pubmed: 25431740
Theriogenology. 2015 Jan 15;83(2):228-37
pubmed: 25442391
Fertil Steril. 2015 Feb;103(2):303-16
pubmed: 25497448
Mol Reprod Dev. 2014 Dec;81(12):1115-35
pubmed: 25511183
Reprod Fertil Dev. 2015 Jul;27(6):906-13
pubmed: 25775380
Biol Reprod. 2015 Jun;92(6):153
pubmed: 25972011
Dev Biol. 2015 Jul 15;403(2):139-49
pubmed: 25981108
Hum Reprod. 2015 Sep;30(9):2138-51
pubmed: 26109618
Reprod Biol Endocrinol. 2015 Aug 16;13:93
pubmed: 26276571
PLoS One. 2015 Aug 27;10(8):e0136473
pubmed: 26313571
Biol Reprod. 2016 Jan;94(1):15
pubmed: 26632608
Reproduction. 2016 Jun;151(6):R103-10
pubmed: 26980808
Theriogenology. 2016 Jul 1;86(1):62-8
pubmed: 27160446
Reproduction. 2016 Dec;152(6):R233-R245
pubmed: 27651517
Nucleic Acids Res. 2016 Dec 15;44(22):11033
pubmed: 27683222
Reproduction. 2017 Mar;153(3):R109-R120
pubmed: 27879344
Nucleic Acids Res. 2017 Jan 4;45(D1):D362-D368
pubmed: 27924014
Proteomes. 2013 Aug 27;1(2):109-127
pubmed: 28250400
Syst Biol Reprod Med. 2017 Apr;63(2):86-99
pubmed: 28301258
J Proteomics. 2018 Mar 20;175:56-74
pubmed: 28385661
In Vivo. 2017 May-Jun;31(3):267-283
pubmed: 28438852
Reprod Fertil Dev. 2018 Jan;30(2):297-306
pubmed: 28679463
Reproduction. 2017 Dec;154(6):881-893
pubmed: 28971896
Mol Hum Reprod. 2017 Dec 1;23(12):827-841
pubmed: 29069483
Int J Mol Sci. 2018 Jan 18;19(1):null
pubmed: 29346283
PLoS One. 2018 Feb 8;13(2):e0192458
pubmed: 29420611
Mol Reprod Dev. 2018 Jul;85(7):579-589
pubmed: 29697878
Reprod Med Biol. 2004 Mar 30;3(1):43-49
pubmed: 29699183
Sci Rep. 2018 Jun 21;8(1):9477
pubmed: 29930262
Reprod Biol Endocrinol. 2019 Mar 6;17(1):29
pubmed: 30841911
Hum Reprod. 1988 May;3(4):425-9
pubmed: 3392176
Proc Natl Acad Sci U S A. 1967 May;57(5):1463-7
pubmed: 5231752
Biochem Med. 1970 Dec;4(5):440-5
pubmed: 5524084
Thromb Res. 1995 Jan 1;77(1):45-54
pubmed: 7701476
Comp Biochem Physiol Comp Physiol. 1994 Feb;107(2):277-82
pubmed: 7907959
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10051-5
pubmed: 8234255
J Biol Chem. 1996 Aug 9;271(32):19409-14
pubmed: 8702628
Mol Reprod Dev. 1996 Mar;43(3):392-402
pubmed: 8868253
J Lipid Res. 1997 Nov;38(11):2216-23
pubmed: 9392419
Equine Vet J Suppl. 1997 Dec;(25):12-6
pubmed: 9593520