ISSN: 2581-5288
Journal of Gynecological Research and Obstetrics
Research Article       Open Access      Peer-Reviewed

Cumulus-oocyte developmental competence: From morphological selection to molecular markers

Nasser Ghanem1*, Romysa Samy1, Dalia Abd-El Rahman Ahmed1, Beshoy SF Khalil1, Eman Kh Kassab1, Md Fakruzzamana2 and Kong IK3

1Animal Production Department, Faculty of Agriculture, Cairo University Research Park, Cairo University, Egypt
2Department of Genetics and Animal Breeding, Faculty of Animal Science and Veterinary Medicine, Patuakhali Science and Technology University, Out Campus, Khanpura, Babuganj, Barishal-8210, Bangladesh
3Division of Applied Life Science (BK21), Graduate School of Gyeongsang National University, Jinju 660-701, Republic of Korea
*Corresponding author: Nasser Ghanem, PhD, Faculty of Agriculture, Department of Animal Production, Cairo University, El-Gamaa street, 12613 Giza, Egypt, Tel: +201002986157; Fax: +20235717355; E-mail:
Received: 31 October, 2020 | Accepted: 10 November, 2020 | Published: 17 November, 2020
Keywords: Omics: In vivo; In vitro; Embryo development; Pregnancy; Fertility

Cite this as

Ghanem N, Samy R, El Rahman Ahmed DA, Khalil BS, Kassab EK, et al. (2020) Cumulus-oocyte developmental competence: From morphological selection to molecular markers. J Gynecol Res Obstet 6(3): 084-086. DOI: 10.17352/jgro.000094

The intrinsic quality of mammalian cumulus-oocyte complexes (COCs) is a determinant factor for pregnancy and fertility in general. The efficiency of assisted reproductive techniques required selection of good quality COCs. Despite the efforts that has been made during the last decades until now worldwide, there is no a reliable non-invasive method or even a reliable marker for oocyte selection. Generally, oocyte quality evaluated based on its morphological features such as thickness, compactness of the cumulus investment and the homogeneity of the ooplasm, which is relatively popular and convenient. However, results derived from this tool are often conflicting largely due to subjectivity and inaccuracy. Thus, the morphological evaluation alone is insufficient to distinguish competent oocytes that have the ability to bring about full-term pregnancy. Biochemical constituents of the follicular fluid represent sensors of the microenvironment condition surrounding the oocyte. Few efforts have given an attention for follicular fluid to be used as oocyte biomarker. Noteworthy, intensive application of assisted reproductive biotechnologies in human and domestic animal species require a good method for selecting good quality oocytes. Recently, global assessment strategies of omics approaches (transcriptomics, miRNAomics, proteomics, lipidomics and metabolomics) have been applied to profile the follicular fluid, oocytes, and granulosa or cumulus cells in several animal species in addition to human. Integration of more than one tool could be a window for finding reliable judging method. Although the great contribution of oocyte quality in controlling fertility the efforts done in finding reliable biological markers is still in the infancy stage. The current short review will shed highlight on attempts has been made in this field.

Oocyte developmental competence

The term “oocyte competence or quality“ is the final measurement of its ability to achieve all cytoplasmic, nuclear and molecular events either in vivo or in vitro to bring a healthy offspring. Sirard, et al. [1] have defined the levels of competence as the ability of oocyte to resume meiosis, cleave following fertilization, develop and differentiate into blastocyst stage, induce pregnancy and finally bring healthy offspring.

Methods used for oocyte selection

There are many criteria (morphological, cellular, molecular) have been proposed to evaluate oocyte quality [2]. The main method of oocyte selection is done based on the morphological evaluation, which score COCs into four classes taken into consideration cytoplasm darkness, number of cumulus layers, extrusion of polar body and spindle formation [2,3]. However, this tool of oocyte selection is inconsistent and sometimes is controversial [2,3], but it a useful preselection tool that could be integrated into other methods. On the other hand, bovine follicle diameter [4] has been shown to be promising tool for oocyte quality screening. Moreover, evaluation of protein activity (glucose-6-phosphate dehydrogenase) was done using brilliant cresyl blue (BCB) staining, which was an effective tool to differentiate good and bad oocyte quality in different animal species. For example, this method was used to screening bovine [5,6], porcine [7], buffalo [8], equine [9], camel [10], goat [11], sheep [12] and mice COCs [13].

A positive relationship between the time of first cleavage post-insemination, and blastocyst rate was reported as effective criteria for bovine oocyte selection [14]. This idea was supported by the work done using time-lapse monitoring system that indicated that oocytes cleaving earliest after IVF being more likely to form blastocyst in good quality that successfully induced pregnancy than their late cleaving counterparts [15].

From molecular point of view, gene expression profiling of cumulus and the oocytes were considered as markers of the bovine oocyte quality [5,16-18]. Expression profile of key genes regulating expansion of cumulus cells (TNFAIP6) and maturation of oocyte (INHBA and FST) were over-expressed in bovine cumulus cells enclosed to COCs matured in vivo [19]. In human, expression of cumulus genes induced by the ovulatory LH peak namely amphiregulin (AREG), cyclooxygenase 2 (COX2 or PTGS2), and steroidogenic acute regulatory protein (STAR) were among molecular markers of COCs nuclear maturation [20,21]. Interestingly, a cumulus expansion regulating gene known as pentraxin 3 (PTX3) was described to be candidate for selecting human oocytes with high ability for pregnancy success [22]. Interestingly, Gasca, et al. [23] have identified regulatory genes (BARD1, RBL2, RBBP7, BUB3 and BUB1B) involved in human COCs maturation.

Distinct sets of candidate genes have identified in bovine oocytes selected according to follicular wave (growth vs. dominance phase) and Brilliant Cresyl Blue (BCB) staining of the first follicular wave [5,24]. Genes regulating protein biosynthesis (RPL24, RPS14, RPS15 and EEF1A1) and mitochondrial activity (ATP5A1) were upregulated in developmentally competent oocyte [5,24]. A cell division cycle 5-like protein (CDC5L) was described to be essential molecular gene for maturation and subsequent embryonic divisions in porcine oocyte selected with BCB test [25]. While, a candidate gene encodes for protein that functions, as zinc transporter (SLC39A8) is upregulated in cumulus cells of bovine [26] and mice oocytes [27]. Recently, STAT3 was identified as a candidate gene of oocyte developmental potential in a study done in our lab [28].

Concluding remarks

Poor oocyte quality reduced fertility rate in vivo and efficiency of in vitro reproductive techniques. Therefore, integration of different methods of COCs selection could be an effective way to increase developmental capacity of oocytes. Meta-analysis of previously discovered molecular markers in the cumulus-oocyte complexes will improve our understanding on the networks of signals that regulate developmental potential and could lead to development of a novel tool for oocyte selection.

  1. Sirard MA, Richard F, Blondin P, Robert C (2006) Contribution of the oocyte to embryo quality. Theriogenology 65: 126-136. Link:
  2. Wang Q, Sun QY (2007) Evaluation of oocyte quality: morphological, cellular and molecular predictors. Reprod Fertil Dev 19: 1-12. Link:
  3. Gordon I (2003) Recovering the bovine oocyte. I Gordon In: Laboratory Production of Cattle Embryos, Cambridge: CAB International/Cambridge University Press 79-111.
  4. Lonergan P, Monaghan P, Rizos D, Boland MP, Gordon I (1994) Effect of follicle size on bovine oocyte quality and developmental competence following maturation, fertilization, and culture in vitro. Molecular Reprod and Dev 37: 48–53. Link:
  5. Alm H, Torner H, Loehrke B, Viergutz T, Ghoneim IM, et al. (2005) Bovine blastocyst development rate in vitro is influenced by selection of oocytes by brilliant cresyl blue staining before IVM as indicator for glucose-6-phosphate dehydrogenase activity. Theriogenology 63: 2194-2205. Link:
  6. Torner H, Ghanem N, Ambros C, Holker M, Tomek W, et al. (2008) Molecular and subcellular characterisation of oocytes screened for their developmental competence based on glucose-6-phosphate dehydrogenase activity. Reproduction 135: 197-212. Link:
  7. El Shourbagy SH, Spikings EC, Freitas M, St John JC (2006) Mitochondria directly influence fertilisation outcome in the pig. Reproduction 131: 233-45. Link:
  8. Manjunatha BM, Gupta PS, Devaraj M, Ravindra JP, Nandi S (2007) Selection of developmentally competent buffalo oocytes by brilliant cresyl blue staining before IVM. Theriogenology 68: 1299-304. Link:
  9. Mohammadi-Sangcheshmeh A, Held E, Ghanem N, Rings F, Salilew-Wondim D, et al. (2011) G6PDH-activity in equine oocytes correlates with morphology, expression of candidate genes for viability, and preimplantative in vitro development. Theriogenology 76: 1215–1226. Link:
  10. Fathi M, Ashry M, Salama A, Badr MR (2017) Developmental competence of Dromedary camel (Camelus dromedarius) oocytes selected using brilliant cresyl blue staining. Zygote 25: 529-536. Link:
  11. Rodríguez-González E, López-Bejar M, Izquierdo D, Paramio MT (2003) Developmental competence of prepubertal goat oocytes selected with brilliant cresyl blue and matured with cysteamine supplementation. Reprod Nutr Dev 43: 179-187. Link:
  12. Catalá MG, Izquierdo D, Uzbekova S, Morató R, Roura M, et al. (2011) Brilliant Cresyl Blue stain selects largest oocytes with highest mitochondrial activity, maturation-promoting factor activity and embryo developmental competence in prepubertal sheep. Reproduction 142: 517-527. Link:
  13. WuYG, Liu Y, Zhou P, Lan GC, Han D, et al. (2007) Selection of oocytes for in vitro maturation by brilliant cresyl blue staining: a study using the mouse model. Cell Res 17: 722-731. Link:
  14. Dinnyes A, Lonergan P, Fair T, Boland MP, Yang X (1999) Timing of the first cleavage postinsemination affects cryosurvival of in vitro produced bovine blastocysts, Mol Reprod Dev 53: 318-324. Link:
  15. Sugimura S, Akai T, Imai KJ (2017) Selection of viable in vitro-fertilized bovine embryos using time-lapse monitoring in microwell culture dishes. Reprod Dev 63: 353-357. Link:
  16. Assidi M, Dufort I, Ali A, Hamel M, Algriany O, et al. (2008) Identification of potential markers of oocyte competence expressed in bovine cumulus cells matured with follicle-stimulating hormone and/or phorbol myristate acetate in vitro. Biol Reprod 79: 209-222. Link:
  17. Bettegowda A, Patel OV, Lee KB, Park KE, Salem M, et al. (2008) Identification of novel bovine cumulus cell molecular markers predictive of oocyte competence: functional and diagnostic implications. Biol Reprod 79: 301-309. Link:
  18. Patel OV, Bettegowda A, Ireland JJ, Coussens PM, Lonergan P, et al. (2007) Functional genomics studies of oocyte competence: evidence that reduced transcript abundance for follistatin is associated with poor developmental competence of bovine oocytes. Reproduction 133: 95-106. Link:
  19. Tesfaye D, Ghanem N, Carter F, Fair T, Sirard MA, et al. (2009) Gene expression profile of cumulus cells derived from cumulus-oocyte complexes matured either in vivo or in vitro. Reprod Fertil Dev 21: 451-461. Link:
  20. Feuerstein P, Cadoret V, Dalbies-Tran R, Guerif F, Bidault R, et al. (2007) Gene expression in human cumulus cells: one approach to oocyte competence. Hum Reprod 22: 3069-3077. Link:
  21. Wyse BA, Fuchs Weizman N, Kadish S, Balakier H, Sangaralingam M, et al. (2020) Transcriptomics of cumulus cells - a window into oocyte maturation in humans. J Ovarian Res 13: 93. Link:
  22. Zhang X, Jafari N, Barnes RB, Confino E, Milad M, et al. (2005) Studies of gene expression in human cumulus cells indicate pentraxin 3 as a possible marker for oocyte quality. Fertil Steril 83: 1169-1179. Link:
  23. Gasca S, Pellestor F, Assou S, Loup V, Anahory T, et al. (2007) Identifying new human oocyte marker genes: a microarray approach. Reprod Biomed Online 14: 175-183. Link:
  24. Ghanem N, Hölker M, Rings F, Jennen D, Tholen E, et al. (2007) Alterations in transcript abundance of bovine oocytes recovered at growth and dominance phases of the first follicular wave. BMC Dev Biol 7: 90. Link:
  25. Liu XM, Wang YK, Liu YH, Yu XX, Wang PC, et al. (2018) Single-cell transcriptome sequencing reveals that cell division cycle 5-like protein is essential for porcine oocyte maturation. J Biol Chem 293: 1767-1780. Link:
  26. Dieci C, Lodde V, Labreque R, Dufort I, Tessaro I, et al. (2016) Differences in cumulus cell gene expression indicate the benefit of a pre-maturation step to improve in-vitro bovine embryo production. Mol Hum Reprod 22: 882-897. Link:
  27. Vigone G, Merico V, Prigione A, Mulas F, Sacchi L, Gabetta M, et al. (2013) Transcriptome based identification of mouse cumulus cell markers that predict the developmental competence of their enclosed antral oocytes. BMC Genomics 14: 380. Link:
  28. Ghanem N, Salilew-Wondim D, Hoelker M, Schellander K, Tesfaye D (2020) Transcriptome profile and association study revealed STAT3 gene as a potential quality marker of bovine gametes. Zygote 13: 1-15. Link:
© 2020 Ghanem N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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