Table 2.
Gene ontology analysis of microarray data
| Gene symbol | Gene name | WT GV | KO GV | Fold‐change | WT MII | KO MII | Fold‐change | (Possible) role in oocyte maturation and early embryo development | References |
|---|---|---|---|---|---|---|---|---|---|
| Elements of signalling pathways activated during oocyte maturation | |||||||||
| Gatsl3 | GATS protein‐like 3 | 9.64 | 8.12 | −2.88 | 9.26 | 8.99 | −1.21 | CASTOR (gatsl3) is an arginine sensor for the mTORC1 pathway. Arginine breaks the CASTOR/GATOR2 complex. GATOR2 activates mTORC1. Activated mTORC1 will phosphorylate translation inhibitor 4E‐BP1, releasing it from eukaryotic translation initiation factor 4E (eIF4E) which is then free to join the translation initiation complex. When the mTORC pathway is inhibited, bovine oocytes are blocked at the M1 stage | Chantranupong et al (2016), Mayer et al (2014) |
| Pygo1 | Pygopus 1 | 8.68 | 6.9 | −3.43 | 8.25 | 6.73 | −2.87 | Pygopus is a Wnt transcriptional component. Knockdown of Axin‐1, a negative regulator of Wnt signalling leads to defective spindles, misaligned chromosomes, PB1 extrusion failure and impaired PN formation. Embryo development is also impacted since maternal Wnt/STOP signalling promotes cell division during early Xenopus embryogenesis. WNT signalling pathway is important for proper oocyte maturation | He et al (2016), Huang et al (2015), Spate et al (2014) |
| Ppp1r14b | Protein phosphatase 1, regulatory (inhibitor) subunit 14B | 12.62 | 11.11 | −2.84 | 12.65 | 11.34 | −2.49 | PP1 is an important protein involved in the cell cycle and controls dephosphorylation of numerous proteins such as proteins phosphorylated by Cdc2 and downstream mitotic kinases. Likely impacts meiotic control | |
| Ppp1r15a | Protein phosphatase 1, regulatory (inhibitor) subunit 15A | 8.26 | 7.29 | −1.96 | 9.12 | 8.17 | −1.92 | ||
| Dusp1 | Dual specificity phosphatase 1 | 11.94 | 10.49 | −2.72 | 12.78 | 11.78 | −2.01 | Dusp1 is able to dephosphorylate MAP kinase, known to be very important in oocyte maturation and meiosis | Liang et al (2007) |
| Nfkbia | Nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha | 9.78 | 8.33 | −2.73 | 9.43 | 7.7 | −3.31 | NFKBIA is a gene involved in maintaining meiotic transcriptional arrest. Inhibits the NF‐κB transcription factor. Change during GV‐MII transition. Highly expressed at embryonic genome activation | Paciolla et al (2011) |
| Pgrmc1 | Progesterone receptor membrane component 1 | 9.16 | 7.97 | −2.27 | 9.53 | 8.01 | −2.86 | P4–PGRMC1 interaction attenuated oocyte meiotic progression and primordial follicle formation by decreasing intra‐oocyte cAMP levels. When PGRMC1 is low, oocytes are not blocked by P4 and mature too fast | Guo et al (2016) |
| Secreted factors | |||||||||
| Cxcl14 | Chemokine (C‐X‐C motif) ligand 14 | 8.08 | 6.99 | −2.13 | 8.59 | 7.5 | −2.13 | Important factor for oocyte maturation in fish | Bobe et al (2006) |
| Adm2 | Adrenomedullin 2 | 11.75 | 10.64 | −2.16 | 12.4 | 11.91 | −1.4 | ADM2 is a novel oocyte‐derived ligand important for the regulation of cell interactions in COCs that functions, in part, by suppressing cumulus cell apoptosis | Chang et al (2011) |
| Transcription translation factors | |||||||||
| Med11 | Mediator complex subunit 11; | 9.84 | 8.28 | −2.94 | 9.78 | 8.39 | −2.62 | Mediator of RNA polymerase II transcription, subunit 11 homologue (S. cerevisiae) | |
| Med29 | Mediator complex subunit 29 | 11.01 | 9.33 | −3.2 | 7.97 | 7.32 | −1.57 | Mediator complex subunit 29 (MED29) is part of a large multiprotein coactivator complex that mediates regulatory signals from gene‐specific activators to general transcription machinery in RNA polymerase II mediated transcription | |
| Sohlh2 | Spermatogenesis and oogenesis specific basic helix‐loop‐helix 2 | 7.18 | 6.06 | −2.18 | 8 | 5.58 | −5.33 | SOHLH2 is a transcription factor that coordinates oocyte differentiation without affecting meiosis I and drives oocyte growth and survival but not meiosis I | Choi et al (2008), Shin et al (2017) |
| Slx2 | Sycp3 like X‐linked | 8.04 | 6.81 | −2.36 | 5.97 | 5.77 | −1.15 | SLX2 might be involved in DNA recombination, synaptonemal complex formation as well as sex body maintenance during meiosis | Shi et al (2013) |
| Prmt5 | Protein arginine N‐methyltransferase 5 | 9.05 | 7.88 | −2.25 | 8.72 | 8.16 | −1.47 | PRMT5 negatively affects cyclin E1 promoter activity. Cyclin E1 is activated during meiosis in Xenopus. Prmt5 is critical in biological function in a wide range of cellular processes including development and methylates histones H2A and H4 in oocytes | Stopa et al (2015), Wilczek et al (2011) |
| Eef1e1 | Eukaryotic translation elongation factor 1 epsilon 1 | 13.39 | 12.26 | −2.19 | 13.24 | 11.78 | −2.76 | DNA damage response. Regulator of translation | Uniprot |
| E2f4 | E2F transcription factor 4 | 13.61 | 12.5 | −2.17 | 14.02 | 13.18 | −1.8 | Regulator of translation | |
| Oxidative stress | |||||||||
| Gstp2 | Glutathione S‐transferase, pi 2 | 12.04 | 10.41 | −3.11 | 10.28 | 9.51 | −1.71 | Important in oxidative stress. A high level of gluthatione transferase is associated with higher oocyte developmental quality. Glutathione S‐transferase is a marker of oocyte maturity in pigs | Paczkowski and Krisher (2010), Rausell et al (2007) |
| Gstp1 | Glutathione S‐transferase, pi 1 | 11.43 | 9.91 | −2.86 | 9.74 | 9.14 | −1.51 | ||
| Spindle assembly | |||||||||
| Pak4 | p21 protein (Cdc42/Rac)‐activated kinase 4 | 11.32 | 10.32 | −2.01 | 12.02 | 11.41 | −1.52 | Ran is a substrate for p21‐activated kinase 4 (PAK4). RanGTP is an important actor of spindle formation and asymmetric division during meiosis | Bompard et al (2013) |
| Ccdc69 | Coiled‐coil domain containing 69 | 14.63 | 13.54 | −2.13 | 14.8 | 13.87 | −1.91 | CCDC69 regulates central spindle assembly | Pal et al (2010) |
| Embryo/trophoblast factors | |||||||||
| Phlda2 | Pleckstrin homology‐like domain, family A, member 2 | 10.3 | 7.56 | −6.7 | 7.7 | 7.05 | −1.57 | PHLDA2 is an imprinted gene, and only the maternal copy is expressed. This gene is associated with placental dysfunction. KO mice exhibit foetal growth deficiency | Frank et al (2002), Jensen et al (2014) |
| Efna1 | Ephrin A1 | 9.73 | 7.34 | −5.24 | 9.05 | 8.02 | −2.04 | Ephrins A1‐4 were expressed in blastocysts. The ephrin A system is involved in regulating contact between blastocysts and endometrium during embryo implantation | Fu et al (2012), Fujii et al (2006) |
| Efna4 | Ephrin A4 | 8.7 | 7.08 | −3.07 | 8.55 | 7.21 | −2.54 | ||
| Efna2 | Ephrin A2 | 8.9 | 7.49 | −2.66 | 8.81 | 7.86 | −1.93 | ||
| Cstb | Cystatin B | 11.81 | 9.44 | −5.17 | 10.85 | 9.5 | −2.55 | The cathepsin–cystatin system plays an important role in trophoblast cell invasion and normal embryonic growth | Nakanishi et al (2005) |
| Prl8a2 | Prolactin family 8, subfamily a, member 2 | 9.51 | 7.17 | −5.05 | 9.12 | 5.93 | −9.16 | In Prl8a2 null tissues, genes expressed in the trophoblast are down‐regulated | Alam et al (2015) |
| Crabp2 | Cellular retinoic acid binding protein II | 12.73 | 10.5 | −4.69 | 12.34 | 10.73 | −3.06 | Altered expression level of endometrial CRABP2 is involved in abnormal endometrium‐trophoblast interaction, which leads to implantation failure | Lee et al (2011) |
| Tlr8 | Toll‐like receptor 8 | 7.34 | 5.49 | −3.61 | 7.15 | 5 | −4.46 | TLR8 is expressed in the trophoblast. Its inhibition suggests that it is necessary for successful establishment of early gestation in ewes | Kaya et al (2017), Ruiz‐Gonzalez et al (2015) |
| Specific MII regulation | |||||||||
| Fgf9 | Fibroblast growth factor 9 | 6.64 | 6.1 | −1.45 | 7.21 | 5.88 | −2.51 | FGF9 counteracts retinoic acid, which promotes entry into meiosis. Its expression increases at MI stage and reaches highest level at the MII stage | Feng et al (2014) |
| Cdc25a | Cell division cycle 25A | 11.59 | 11.55 | −1.03 | 12.31 | 11.18 | −2.19 | Its expression increases significantly at the MII stage. Cdc25a is crucial in the MI‐MII transition and its down‐regulation results in fewer oocytes resuming meiosis and reaching MII | Solc et al (2008) |