Cumulus cell gene expression is associated with oocyte developmental quality and influenced by patient and treatment characteristics.
BACKGROUND
Gene expression of cumulus cells (CC) could predict oocyte developmental quality. Knowledge of the genes involved in determining oocyte quality is scanty. The aim was to correlate clinical and biological characteristics during ovarian stimulation with the expression of 10 selected genes in CC.


METHODS
Sixty-three ICSI patients were stimulated with GnRH-agonist plus highly purified hMG (n = 35) or recombinant FSH (n = 28). Thirteen variables were analyzed: Age, BMI, duration of stimulation, serum concentrations of progesterone, 17beta-estradiol, FSH and LH on day of hCG, Ovarian Response, Oocyte Maturity, 2 pronuclei and three embryo morphology related variables: > or =7 cells, Low Fragmentation, Good Quality Embryos score. Expression of HAS2, VCAN, SDC4, ALCAM, GREM1, PTGS1, PTGS2, DUSP16, SPROUTY4 and RPS6KA2 was analyzed in pooled CC using quantitative PCR, and the relationship to the 13 variables was evaluated by multivariable analysis.


RESULTS
All 10 genes are expressed at oocyte retrieval, with PTGS1, SPROUTY4, DUSP16 and RPS6KA2 described in human ovary for the first time. The three variables that correlated most often with differential expression were Age, BMI and serum FSH level. Significant correlation was found with Oocyte Maturity (VCAN, P < 0.005), Low Fragmentation (RPS6KA2, P < 0.05), Embryos with > or =7 cells (ALCAM and GREM1, P < 0.05). The expression of the other genes was also correlated to oocyte developmental quality but to a less extent. SDC4, VCAN, GREM1, SPROUTY4 and RPS6KA2 showed gonadotrophin preparation-dependent expression and/or interactions (all P < 0.05).


CONCLUSIONS
The expression of ovulation related genes in CC is associated with patient and treatment characteristics, oocyte developmental potential and differs with the type of gonadotrophin used.
Adriaenssens
T
T
Follicle Biology Laboratory, Vrije Universiteit Brussel, Laarbeeklaan 101, B 1090 Brussels, Belgium. tom.adriaenssens@uzbrussel.be
Wathlet
S
S
Segers
I
I
Verheyen
G
G
De Vos
A
A
Van der Elst
J
J
Coucke
W
W
Devroey
P
P
Smitz
J
J
D000328:Adult; D001483:Base Sequence; D015992:Body Mass Index; D054885:Cumulus Cells / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D054637:Dual-Specificity Phosphatases / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008596:Menotropins / Q000008:administration & dosage; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009865:Oocytes / Q000254:growth & development* / Q000378:metabolism*; D010062:Ovulation Induction / Q000379:methods; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D020554:Sperm Injections, Intracytoplasmic
D017931:DNA Primers; D043373:Follicle Stimulating Hormone, Human; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C499038:SPRY4 protein, human; D008596:Menotropins; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; D054639:Mitogen-Activated Protein Kinase Phosphatases; C439065:DUSP16 protein, human; D054637:Dual-Specificity Phosphatases