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Bar‐Ami, Shalom; Gitay-Goren, Hela

doi:10.1023/a:1009465218688

Cited by 4 publications

(1 citation statement)

References 33 publications

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“…Specific functions of the somatic cells from the pre-ovulatory follicles just prior to ovulation (e.g. progesterone and oestrogen production from the cumulus-oocyte-complex (COC) [ 3 ] and expression levels of specific genes in the mural granulosa cells (MGC) and cumulus cells (CC) have been shown to reflect the developmental competence of the corresponding oocyte. Several authors have used a single gene approach by analyzing few genes by RT-PCR [ 4 – 7 ], while others have used global gene expression profiling analysis to find differences in somatic cell gene expression between cells connected to competent and non-competent oocytes [ 8 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

Competence Classification of Cumulus and Granulosa Cell Transcriptome in Embryos Matched by Morphology and Female Age

et al. 2016

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ObjectiveBy focussing on differences in the mural granulosa cell (MGC) and cumulus cell (CC) transcriptomes from follicles resulting in competent (live birth) and non-competent (no pregnancy) oocytes the study aims on defining a competence classifier expression profile in the two cellular compartments. Design: A case-control study. Setting: University based facilities for clinical services and research. Patients: MGC and CC samples from 60 women undergoing IVF treatment following the long GnRH-agonist protocol were collected. Samples from 16 oocytes where live birth was achieved and 16 age- and embryo morphology matched incompetent oocytes were included in the study.MethodsMGC and CC were isolated immediately after oocyte retrieval. From the 16 competent and non-competent follicles, mRNA was extracted and expression profile generated on the Human Gene 1.0 ST Affymetrix array. Live birth prediction analysis using machine learning algorithms (support vector machines) with performance estimation by leave-one-out cross validation and independent validation on an external data set.ResultsWe defined a signature of 30 genes expressed in CC predictive of live birth. This live birth prediction model had an accuracy of 81%, a sensitivity of 0.83, a specificity of 0.80, a positive predictive value of 0.77, and a negative predictive value of 0.86. Receiver operating characteristic analysis found an area under the curve of 0.86, significantly greater than random chance. When applied on 3 external data sets with the end-point outcome measure of blastocyst formation, the signature resulted in 62%, 75% and 88% accuracy, respectively. The genes in the classifier are primarily connected to apoptosis and involvement in formation of extracellular matrix. We were not able to define a robust MGC classifier signature that could classify live birth with accuracy above random chance level.ConclusionWe have developed a cumulus cell classifier, which showed a promising performance on external data. This suggests that the gene signature at least partly include genes that relates to competence in the developing blastocyst.

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Section: Introductionmentioning

confidence: 99%

Competence Classification of Cumulus and Granulosa Cell Transcriptome in Embryos Matched by Morphology and Female Age

et al. 2016

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A possible role of progesterone receptor in mouse oocyte in vitro fertilization regulated by norethisterone and its reduced metabolite

et al. 2008

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Specific genes are selectively expressed between cumulus and granulosa cells from individual human pre-ovulatory follicles

Grøndahl

Andersen

Bogstad

et al. 2012

MHR: Basic Science of Reproductive Medicine

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During folliculogenesis, the granulosa cells differentiate into two cell types: cumulus cells (CCs) and mural granulosa cells (MGCs). The objective of the study was to generate and compare the transcriptomes of MGCs and CCs from the pre-ovulatory follicle to characterize the detailed profile of the two cell populations shortly before ovulation. Twenty-one IVF/ICSI patients undergoing controlled ovarian stimulation (COS) donated CCs and MGCs from individual follicles containing metaphase II oocytes. Cells were prepared immediately after recovery and mRNA was isolated for whole-genome gene expression analysis and reverse transcriptase-polymerase chain reactions. Paired (within the individual follicle) comparisons between the CC and MGC expression profiles were performed and corrected for multiple comparisons. A total of 1562 genes were differentially expressed by >2-fold (P < 0.01) in the two cell types. Of these, 156 genes were >8-fold changed and represented specialized cellular functional categories such as inflammatory response, extracellular matrix and cell-cell communication, whereas the 1406 genes were 2-8-fold changed and represented functional categories such as proliferation and lipid metabolism. Transcripts not previously linked to the follicle were found to be differentially expressed between CCs and MGCs, suggesting specialized function in these compartments, e.g. pepsinogen A was selectively expressed in MGCs, whereas ryanodine receptor-2 (RYR2) was selectively expressed in CCs. Positive correlations were present between expression levels of RYR2 and the amphiregulin and gap-junction proteins. In conclusion, the transcriptomes of corresponding CCs and MGCs from individual pre-ovulatory follicles clearly revealed two distinct cell types. New as well as known genes representing specific cell functions close to ovulation were highlighted.

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Abstract: Addition of pregnenolone increased progesterone secretion and 3 beta-HSD more efficiently in the higher-progesterone-secreting cumuli. Coculture of two COCs instead of one led to a higher fertilization rate and greater progesterone secretion.

Cited by 4 publications

References 33 publications

Competence Classification of Cumulus and Granulosa Cell Transcriptome in Embryos Matched by Morphology and Female Age

Competence Classification of Cumulus and Granulosa Cell Transcriptome in Embryos Matched by Morphology and Female Age

A possible role of progesterone receptor in mouse oocyte in vitro fertilization regulated by norethisterone and its reduced metabolite

Specific genes are selectively expressed between cumulus and granulosa cells from individual human pre-ovulatory follicles

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