Gene expression profiles of single human mature oocytes in relation to age.
BACKGROUND
The development competence of human oocytes declines with increasing age. The objective of this study was to investigate the effect of age on gene expression profile in mature human oocytes.


METHODS
mRNA was isolated for whole genome gene expression microarray analysis from metaphase II (MII) oocytes donated by IVF or ICSI patients [10 women aged <36 years (younger) and five women aged 37-39 years (both inclusive) (older)] undergoing controlled ovarian stimulation. The oocytes were donated and prepared immediately after recovery from the follicle. RT-PCR on additional four younger and two older oocytes confirmed the array analysis.


RESULTS
On the basis of 15 independent replicates of single MII oocytes, 7470 genes (10 428 transcripts) were identified as present in the MII oocytes. Of these, 342 genes showed a significantly different expression level between the two age groups; notably, genes annotated to be involved in cell cycle regulation, chromosome alignment (e.g. MAD2L1 binding protein), sister chromatid separation (e.g. separase), oxidative stress and ubiquitination. The top signaling network affected by age was 'cell cycle and organism development' (e.g. SMAD2 and activin B1 receptor).


CONCLUSIONS
There is a substantial difference between younger and older oocytes in the transcriptional level of genes involved in central biological functions of the oocytes, thus providing information on processes that may be associated with the ageing phenomenon and possibly contributing to decreased fertility.
University Hospital Copenhagen, Rigshospitalet, Fertility Clinic, Copenhagen, Denmark. marie.louise.groendahl@rh.regionh.dk
M L
ML
Grøndahl
C
C
Yding Andersen
J
J
Bogstad
F C
FC
Nielsen
H
H
Meinertz
R
R
Borup
D000328:Adult; D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D002453:Cell Cycle; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D066298:In Vitro Techniques; D008540:Meiosis; D008677:Metaphase; D008938:Mitosis; D020411:Oligonucleotide Array Sequence Analysis; D018587:Oocyte Donation; D009865:Oocytes / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D018384:Oxidative Stress; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D054875:Ubiquitination
D017931:DNA Primers