Review Article

Gene Expression Profiling of Human Oocytes Developed and Matured In Vivo or In Vitro

Table 2

Gene expression profiling of human oocytes using microarrays.

Analyses of oocyte gene expression by microarrays
Analyzed oocytesExpression of genesFunctions of analyzed genesStudy

Seventy seven in vivo matured oocytes at different stages of maturity: 20 GV oocytes (7 patients), 20 MI oocytes
(7 patients), 37 MII oocytes, cumulus cells
Identification of new potential regulators and marker genes involved in the human in vivo oocyte maturationTranscription regulation, DNA repair, cell cycle checkpoint Gasca et al., 2007 [2]

Individual MII oocytes and groups of 5 MII oocytes1,361 transcripts expressed in oocytesApoptosis, cell cycle, circadian rhythms, cytoskeleton, secretory pathways, exocytosis, endocytosis, kinases, membrane receptors, ion channels, mitochondria, structural nuclear proteins, phospholipases, protein degradation and synthesis, secreted proteins, signaling pathways, DNA, chromatin, RNA, transcription, and others Bermúdez et al., 2004 [14]

Groups of 10 MII oocytes from women aged <35 years
in comparison to 10 different normal human somatic tissues
5,331 transcripts significantly up-regulated and 7,074 transcripts significantly down-regulated in human oocytesUp-regulated TGF-β pathway,
DNA, RNA and protein metabolism, transcription regulation,
chromatin modification
Kocabas et al., 2006 [15]

Groups of 20 GV, 20 MI, and 16 MII oocytes Oocytes expressed in average 8,728 genes. The lowest number of expressed genes in MII oocytes (5,633) and highest in GV oocytes (10,892)Genes specifically expressed in germinal cells and oocytes, meiosis, components of the maturation-promoting factor (MPF), spindle checkpoint, transforming growth factor-beta superfamily, chromatin remodelingAssou et al., 2006 [16]

Nine MII and GV
oocytes, preimplantation embryos
Human oocytes are low RNA template samples and an amplification step is required to provide sufficient labeled RNA as a microarray target (PCR and serial analysis of gene expression SAGE, microarrays)Neilson et al., 2000 [20]
Dobson et al., 2004 [21]

Seven individuals: 5 GV (primary) and 2 MII (secondary) oocytes and 15 preimplantation embryosDown-regulation of genes in preimplantation embryos in comparison with oocytesOocyte maturation and embryo developmentDobson et al., 2004 [21]

Single and pooled GV oocytesOocytes need to be pooled for the starting template for each array and sufficient microarray experiments performed to minimize the variance associated with processingJones et al., 2007
[22]

Four individual MII oocytes and four 4-cell and three 8-cell embryos A total of 631 genes exhibited differential expression in oocytes and embryos. In oocytes 184 genes were expressed more than twofold above the median value. Only two genes were at least twofold below the median valueInterconversion of lactate and pyruvate, lactate dehydrogenase, oocyte maturation, embryo developmentLi et al., 2006
[18]

Immature oocytes from primordial, intermediate, and primary folliclesA total of 6,301 unique genes were significantly expressed; extraordinary high expression levels of TMEFF2, OPHN1 and ATP6; expression of oocyte- or germline-specific genesRNA binding, translation initiation structural molecule activity, BMP receptors, activin receptors, IGFI receptor, fibroblast growth factors, different enzymes Markholt et al., 2012 [23]

Seventy six GV oocytes from 55 donor patients, hESCs, and human foreskin fibroblasts10,183 genes were expressed in GV oocytes including oocyte-specific genes. Distinct sets of genes were detected in oocytes, hESCs and fibroblastsIn GV oocytes 4 signaling pathways—MOS-MPF, transforming growth factor-beta, Wnt, and Notch, oocyte maturity, embryo developmentZhang et al., 2007
[24]

GV and MII oocytes, hESCs, somatic tissuesIdentified a common oocyte/hESC gene expression profileCell cycle, enzymes involved in general cell metabolism, nucleoside synthesis, DNA repair, cell cycle regulatory machinery, regulation of the topologic state of DNA, mitotic spindle assembly checkpoint, pluripotency, chromatin remodelling, transcription factors, ubiquitination, and proteasome pathwaysAssou et al., 2009
[25]

GV oocytes, MII oocytes matured in vivo and in vitro GV, in vivo matured MII oocytes, and in vitro matured MII oocytes expressed 12,219, 9,735, and 8,510 genes. There was an extensive overlap among the all three groups of oocytes, but also some significant differences. There were some immature GV oocyte patterns of gene expression, which still persisted in in vitro matured oocytesNuclear maturity, cytoplasmic functions expressed in an immature manner, cellular storage and homeostasis Wells and Patrizio, 2008
[26]

GV oocytes, MII oocytes matured in vivo and in vitro More than 2,000 genes were expressed at more than 2-fold higher levels in oocytes matured in vitro than those matured in vivo Transcription, the cell cycle and its regulation, transport and cellular protein metabolismJones et al., 2008
[27]

Fresh, slowly frozen, and vitrified MII oocytesOocyte slow freezing and vitrification negatively affected the gene expression profile of human oocytes in comparison with fresh controlsChromosomal structure maintenance, cell cycle regulation, genes of the ubiquitination pathwayMonzo et al., 2012 [28]

Thirty nine MII oocytes with total fertilization failure and control oocytesMisexpression of several genes, characterized by important fold changes in oocytes with total fertilization failureMeiosis, cell growth, and apoptosis control
Gasca et al., 2008
[29]

Fifteen GV oocytes which matured to MII stage overnight and their polar bodiesTranscripts that were present in greater abundance in the single oocytes were also detected in qPCR replicates from single polar bodies, except oocyte-specific H1FOO Klatsky et al., 2010 [30]

Single MII oocytes and single polar bodies after biopsyHuman polar bodies reflected the oocyte transcript profile.
5,256 mRNAs, or 97%, including miRNAs were expressed in both oocytes and polar bodies
Reich et al., 2011
[31]

MII oocytes of younger
(<32 years) and older women (>40 years)
Found that the global gene expression profiles in oocytes are related to female age. Genes were down-regulated in older womenCell cycle regulation, cytoskeletal structure, energy pathways, transcription control, and stress responsesSteuerwald et al., 2007 [32]

Single MII oocytes of younger (<34 years) and older women (37–39 years)7,470 genes (10,428 transcripts) were expressed in oocytes; 342 genes were expressed at significantly different expression levels between the two age groups of patientsCell cycle regulation, chromosome alignment, sister chromatid separation, oxidative stress and ubiquitination, the signaling network of genes for cell cycle and organism development Grøndahl et al., 2010 [33]

Seven MII oocytes (three normal and four aneuploid) and their polar bodies after biopsyAt comparative genomic hybridization 327 genes were differently expressed in both groups of oocytes; the relation between mRNA transcript numbers and female ageMeiotic spindle assembly, chromosome alignment, production of cell surface, or excretory molecules.Fragouli et al., 2010 [34]