Cumulus cell gene expression is associated with oocyte developmental quality and influenced by patient and treatment characteristics

Adriaenssens, Tom; Wathlet, Sandra; Segers, Ingrid; Verheyen, Greta; Vos, Anick De; Elst, Josiane Van Der; Coucke, Wim; Devroey, Paul; Smitz, Johan

doi:10.1093/humrep/deq049

Cited by 125 publications

(144 citation statements)

References 33 publications

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“…Given the role of CCs in oocyte maturation support, that they actively influence the oocyte's acquisition of developmental competence, and that many cumulus function are regulated by the oocyte [14], the chemical analysis of these cells may be a promising approach for the non-invasive assessment of oocyte competence, embryo development potential and future pregnancy. Several groups have been searching for new markers of oocyte competence and pregnancy outcome in these cells [1,3]. However, to our knowledge, this work is the first time that analysis of the lipid profile of CCs by MALDI-TOF MS has been studied.…”

Section: Discussionmentioning

confidence: 99%

The follicular microenviroment as a predictor of pregnancy: MALDI-TOF MS lipid profile in cumulus cells

Montani

Cordeiro

Regiani

et al. 2012

J Assist Reprod Genet

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Purpose This research proposed to study the changes in lipid composition in cumulus cells (CCs) from women who achieved pregnancy compared with women who did not, after in vitro fertilization treatment. This approach has the potential to provide novel information on the lipid metabolism of the CCs and as an additional method to predict pregnancy. Method Fifty-four samples from couples with tubal and male factor infertility and where the female partner was age 35 or younger were divided in two groups according to their level of hCG 14 days after embryo transfer as follows: (1) 23 samples in pregnant group and (2) 31 samples in non-pregnant group. Lipid extraction was performed by the Bligh-Dyer protocol, and lipid profiles were obtained by MALDI-TOF MS. Mass spectra data were processed with MassLynx, and statistical analysis was performed using MarkerLynx extended statistic. OPLS-DA model was built. Results S-plot Analysis revealed three ions as potential markers in the pregnant group, and five ions in the nonpregnant group. These ions were identified in the human metabolome database (HMDB) as phosphatidylcholine in the pregnant group and as phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol species in the non-pregnant group. These lipids might be involved in cell proliferation and differentiation, apoptosis and GAP junction regulation. Conclusion We conclude that MALDI-TOF MS can be used as an informative and fast analytical strategy to obtain and study the lipid profile of cumulus cells and can potentially be used as a supporting tool to predict pregnancy based on the metabolic state of the CCs.

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Section: Discussionmentioning

confidence: 99%

The follicular microenviroment as a predictor of pregnancy: MALDI-TOF MS lipid profile in cumulus cells

Montani

Cordeiro

Regiani

et al. 2012

J Assist Reprod Genet

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“…Previous researches have proved that different gene expressions of CCs could indicate oocyte competence or predict the efficiency of embryo development and pregnancy outcome (McKenzie et al 2004, Zhang et al 2005, Feuerstein et al 2007, Assou et al 2008, van Montfoort et al 2008, Kenigsberg et al 2009, Adriaenssens et al 2010, Assou et al 2010. Nevertheless, among all these previous studies on the gene expression profiles of human CCs, only one study (Ouandaogo et al 2011) has highlighted the distinct gene expression of human CCs isolated from oocytes at the GV, MI, and MII stages, while others have mainly focused on CCs surrounding the oocytes at MII stage.…”

Section: Introductionmentioning

confidence: 99%

Differences in the transcriptional profiles of human cumulus cells isolated from MI and MII oocytes of patients with polycystic ovary syndrome

Huang¹,

Hao²,

Shen³

et al. 2013

Reproduction

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Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. The abnormalities of endocrine and intra-ovarian paracrine interactions may change the microenvironment for oocyte development during the folliculogenesis process and reduce the developmental competence of oocytes in PCOS patients who are suffering from anovulatory infertility and pregnancy loss. In this microenvironment, the cross talk between an oocyte and the surrounding cumulus cells (CCs) is critical for achieving oocyte competence. The aim of our study was to investigate the gene expression profiles of CCs obtained from PCOS patients undergoing IVF cycles in terms of oocyte maturation by using human Genome U133 Plus 2.0 microarrays. A total of 59 genes were differentially expressed in two CC groups. Most of these genes were identified to be involved in one or more of the following pathways: receptor interactions, calcium signaling, metabolism and biosynthesis, focal adhesion, melanogenesis, leukocyte transendothelial migration, Wnt signaling, and type 2 diabetes mellitus. According to the different expression levels in the microarrays and their putative functions, six differentially expressed genes (LHCGR, ANGPTL1, TNIK, GRIN2A, SFRP4, and SOCS3) were selected and analyzed by quantitative RT-PCR (qRT-PCR). The qRT-PCR results were consistent with the microarray data. Moreover, the molecular signatures (LHCGR, TNIK, and SOCS3) were associated with developmental potential from embryo to blastocyst stage and were proposed as biomarkers of embryo viability in PCOS patients. Our results may be clinically important as they offer a new potential strategy for competent oocyte/embryo selection in PCOS patients.

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“…Evaluation of cumulus or granulosa cells to identify additional factors associated with oocyte/embryo quality and positive IVF outcomes has been performed [49,50]. For example, large-scale microarray analyses have identified a correlations between ferridoxin (FDX1), aromatase (CYP19A1), and CDC42 levels in follicular cells and oocyte competence [51], and between BCL2L11, PCK1 and NFIB levels in cumulus cells and embryo potential and the likelihood of a successful pregnancy [52].…”

Section: Discussionmentioning

confidence: 99%

Relative expression of genes encoding SMAD signal transduction factors in human granulosa cells is correlated with oocyte quality

Kuo

Fan

Ambartsumyan

et al. 2011

J Assist Reprod Genet

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Purpose To determine the expression of SMAD transcripts in human granulosa cells. Methods Luteinized mural granulosa cells were harvested from forty women undergoing oocyte retrieval, and RNAs were isolated. SMAD expression levels were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (q-RTPCR). Results SMAD1-7 and 9 are expressed in human granulosa cells, with SMAD2, 3 and 4 showing the highest expression levels. Peak estradiol (E2) levels correlated with the number of oocytes retrieved during IVF. Oocyte number showed no correlation with SMAD expression levels or ratios. Fertilization rates also did not correlate with the expression levels of individual SMADs, but did correlate with higher SMAD4:SMAD3 ratios (p=0.0062) and trended with SMAD4:SMAD2 (p=0.0698). Conclusions SMAD transcripts are differently expressed in human granulosa cells, where they may mediate TGF-beta superfamily signaling during folliculogenesis and ovulation. Further, the relative expression ratios of SMAD2, 3 and 4 may differentially affect fertilization rate.

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Cumulus cell gene expression is associated with oocyte developmental quality and influenced by patient and treatment characteristics

Abstract: 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.

Cited by 125 publications

References 33 publications

The follicular microenviroment as a predictor of pregnancy: MALDI-TOF MS lipid profile in cumulus cells

The follicular microenviroment as a predictor of pregnancy: MALDI-TOF MS lipid profile in cumulus cells

Differences in the transcriptional profiles of human cumulus cells isolated from MI and MII oocytes of patients with polycystic ovary syndrome

Relative expression of genes encoding SMAD signal transduction factors in human granulosa cells is correlated with oocyte quality

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