Transcriptomic profiling of human oocytes: association of meiotic aneuploidy and altered oocyte gene expression.
The ability to identify oocytes with the greatest potential for producing a viable embryo would be of great benefit to assisted reproductive treatments. One of the most important defects affecting oocytes is aneuploidy. Aneuploidy is also closely related with advancing maternal age, a phenomenon not well understood. This study combined a comprehensive cytogenetic investigation of 21 oocytes with a detailed assessment of their transcriptome. The first polar body was removed from all oocytes and aneuploidy assessed using comparative genomic hybridization. Preliminary mRNA transcript data were produced with the use of microarrays for seven of the corresponding oocytes (three normal and four aneuploid). The results obtained for normal and aneuploid oocytes were compared and 327 genes were found to display statistically (P < 0.05) significant differences in transcript levels. Ninety-six of these genes were further assessed in seven aneuploid and seven normal oocytes using real-time PCR. The results indicated that aneuploidy is associated with altered transcript levels affecting a subset of genes. A link between mRNA transcript numbers and age was also observed. The possibility that different transcript levels in the oocyte have an impact on cellular pathways remains to be proven. However, it may be significant that some of the highlighted genes produce proteins involved in spindle assembly and chromosome alignment. Additionally, several genes with altered amounts of transcript produce cell surface or excretory molecules, and could potentially serve as targets for non-invasive oocyte aneuploidy assessment.
Fragouli
E
E
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK. elpida.fragouli@obs-gyn.ox.ac.uk
Bianchi
V
V
Patrizio
P
P
Obradors
A
A
Huang
Z
Z
Borini
A
A
Delhanty
J D A
JD
Wells
D
D
D000328:Adult; D000782:Aneuploidy; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008423:Maternal Age; D008540:Meiosis / Q000235:genetics*; D046228:Microarray Analysis; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D027724:Reproductive Techniques, Assisted; D020133:Reverse Transcriptase Polymerase Chain Reaction