Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF.
BACKGROUND
A biochemical marker for embryo development would increase the chance of a successful pregnancy with IVF by optimizing oocyte and embryo selection, and allow fewer embryos to be transferred. In this study, we correlated cumulus granulosa cell gene expression of hyaluronic acid synthase 2 (HAS2), cyclooxygenase 2 (COX2; PTGS2) and gremlin (GREM1) with subsequent embryo development in search of a parameter for embryo selection.


METHODS
Cumulus cell gene expression was determined prospectively on eight consecutive patients undergoing IVF with ICSI. Immediately following oocyte retrieval, the cumulus was stripped from the oocyte, and cumulus gene expression for PTGS2, HAS2 and GREM1 was assessed using a one-step real-time quantitative RT-PCR assay. Oocyte quality, fertilization and embryo morphology were correlated to relative gene expression.


RESULTS
Gene expression data were available on cumulus cells from 108 oocytes that developed into 70 embryos (64.8% fertilization rate). Cumulus PTGS2, HAS2 and GREM1 expression was higher from oocytes that developed into higher quality embryos (grades 3, 4 and 5) compared with lower quality embryos (grades 1 and 2) (P<0.05, P<0.001 and P<0.001, respectively). HAS2 and GREM1 expression was also higher from the cumulus surrounding oocytes that gave rise to higher grade embryos (P<0.001). The expression of PTGS2 and HAS2 was 6-fold higher, and that of GREM1 was 15-fold higher in cumulus yielding higher grade embryos versus lower grade embryos.


CONCLUSIONS
PTGS2, HAS2 and GREM1 gene expression correlates to morphological and physiological characteristics and provides a novel approach to predict human embryo development. Ultimately, with better predictors of follicular and embryonic health, higher quality embryos can be selected and transferred, reducing higher order pregnancy rates.
Department of Obstetrics, Baylor College of Medicine, Houston, TX 77030, USA.
L J
LJ
McKenzie
S A
SA
Pangas
S A
SA
Carson
E
E
Kovanci
P
P
Cisneros
J E
JE
Buster
P
P
Amato
M M
MM
Matzuk
D000328:Adult; D002097:C-Reactive Protein; D051546:Cyclooxygenase 2; D004622:Embryo, Mammalian / Q000502:physiology*; D005260:Female; D005307:Fertilization in Vitro; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000235:genetics; D006107:Granulosa Cells / Q000502:physiology*; D006801:Humans; D000076002:Hyaluronan Synthases; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins; D011237:Predictive Value of Tests; D011247:Pregnancy; D018873:Pregnancy Rate; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012372:ROC Curve; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
D002097:C-Reactive Protein; D051546:Cyclooxygenase 2; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C486399:GREM1 protein, human; C496540:PTGS2 protein, human; C101754:HAS2 protein, human