TABLE 1.
Summary table of eight cumulus biomarkers and their significance in assessing oocyte development competency and/or IVF outcomes.
| Authors | Biomarkers | Oocyte maturation event | Detection method | Sample size | Key findings |
| Maman et al. (2012) | LHR | Nuclear maturation | RT-PCR | Granulosa cells from 70 IVF patients and 20 IVM (in vitro Maturation) patients | Expression of LHR is higher in metaphase II oocytes than in metaphase I and germinal vesicle oocytes (P < 0.05), but overexpression is associated with low fertilization capacity (P < 0.05) |
| Wiweko et al. (2019) | LHR | RT-PCR | Granulosa cells from 10 poor responder IVF patients and 20 non-poor responder patients | In poor responders: Positive correlation of LHR expression with oocyte maturity (r = 0.267), oocyte morphology (r = 0.267), and fertilization rate (r = 0.430) In non-poor responders: Negative correlation of LHR expression with oocyte maturity (r = −0.552), morphology (r = −0.164), and fertilization rate (r = −0.340) |
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| Gode et al. (2011) | BMP15, GDF9 | Western blot | 81 individually derived cumulus-oocyte complexes (COCs) and follicular fluids collected from the first retrieved follicle of 81 IVF/ICSI patients | Nuclear maturation of oocytes (P < 0.05) and quality of embryos (P < 0.05) are significantly correlated with the level of mature GDF9 in follicular fluid | |
| Li et al. (2014) | BMP15, GDF9 | qPCR. | 2,426 COCs from 196 IVF/ICSI patients | Expression of GDF9 and BMP15 mRNAs in cumulus granulosa cells were highly correlated with oocyte maturation, fertilization, and embryo quality (P < 0.05). Pregnancy predicting capacity is evident (GDF9 with 4.82 cut-off value, 82% sensitivity, and 64% capacity; BMP15 with 2.60 cut-off value, 78% sensitivity, and 52% capacity) | |
| Hasegawa et al. (2007) | Cx43 | Apoptosis | RT-PCR | 105 CC samples from 29 IVF/ICSI patients | No relationship of Cx43 with fertilization and cleavage rate. Cx43 expression was significantly lower in good morphology cleavage-stage embryos compared to other groups (P = 0.035) |
| Wang et al. (2009) | Cx43 | RT-PCR, Immunofluorescence microscopy, Western blot, gap junctional coupling assay | Cumulus cell (CC) samples from 115 patients | A positive correlation (P < 0.05) of Cx43 level with embryo quality (cleavage rate and morphology). Cx43 level is significantly higher in patients who became pregnant (P < 0.01) | |
| Salehi et al. (2017) | Pro apoptosis proteins (Caspase-3, Caspase-7) | RT-PCR | 100 CC from 20 PCOS IVF patients and 100 cumulus cells from 20 normal IVF patients (control group) | Caspase-3 and Caspase-7 expression were higher in PCOS patients. Significant correlation of embryo quality with Caspase-3 (P = 0.0016) and Caspase-7 (P = 0.084) expression in PCOS patients | |
| Devjak et al. (2012) | SERPINE2 | Extracellular matrix remodeling | Microarray, Quantitative real-time PCR (qPCR) | 46 CC samples from 21 patients | Positive correlation between microarray and qPCR data (r = 0.98, P = 0.02) indicating lower expression of SERPINE2 mRNA in cumulus cells of mature oocytes than in immature oocytes |
| Li et al. (2015) | SERPINE2 | RT-PCR | 308 COC samples from 40 IVF patients (53 immature oocytes and 255 mature oocytes) | Expression of SERPINE2 was significantly lower in cumulus cells of mature oocytes than in immature oocytes (P = 0.0002) | |
| Yung et al. (2010) | ADAMTS-1 | Quantitative real-time PCR (qRT-PCR), Western blot | CC from 25 patients | ADAMTS-1 is associated with larger and more mature follicles and is positively correlated with oocyte fertilization capacity | |
| Kordus et al. (2019) | PAPPA | Steroid metabolism | RT-PCR | 163 CC samples from 15 patients | PAPPA expression level is significantly higher in CC of oocytes that led to euploid embryos resulting in a live birth (P < 0.05, OR = 4.591) |
| Wyse et al. (2020) | 42 potential oocyte maturation biomarkers | Transcriptomics of cumulus cells | RNA sequencing, differential expression, pathway analysis, Quantitative real-time PCR (qPCR) | 22 COCs from 11 patients | Differentially expressed genes identified between oocytes of different maturity |