Top

Reproductive Biology and Endocrinology

Published in:

Open Access 01-12-2015 | Research

Correlation of cumulus gene expression of GJA1, PRSS35, PTX3, and SERPINE2 with oocyte maturation, fertilization, and embryo development

Authors: Sheng-Hsiang Li, Ming-Huei Lin, Yuh-Ming Hwu, Chung-Hao Lu, Ling-Yu Yeh, Ying-Jie Chen, Robert Kuo-Kuang Lee

Published in: Reproductive Biology and Endocrinology | Issue 1/2015

Abstract

Background

GJA1 and PTX3 were proposed as gene markers for oocyte and embryo developmental competence, while SERPINE2 was reported to be associated with pregnancy outcome. PRSS35, which is exclusively expressed in the ovary, may be correlated with oocyte competence. This study was conducted to evaluate the correlation of cumulus GJA1, PRSS35, PTX3, and SERPINE2 gene expression levels with oocyte maturation, fertilization, and early embryo development.

Methods

In total, 308 cumulus cell samples separated from individual cumulus–oocyte complex were obtained from 40 patients undergoing the intracytoplasmic sperm injection treatment procedure. Gene expression levels (mRNA levels) in cumulus cells were assessed using quantitative real-time polymerase chain reaction.

Results

Gene expression levels of GJA1 and SERPINE2 in cumulus cells surrounding mature oocytes were significantly lower than those in cumulus cells enclosing immature oocytes. PRSS35 mRNA levels in cumulus cells of fertilized oocytes were significantly higher than those in cumulus cells of unfertilized oocytes. GJA1 and SERPINE2 seemed to express higher mRNA levels, while PRSS35 showed lower expression in cumulus cells of oocytes that developed into embryos with good morphology; however, the expression levels of all three genes and PTX3 showed no significant differences between embryos with good or poor morphology.

Conclusions

GJA1 and SERPINE2 represent potential gene markers associated with oocyte maturation. PRSS35 may be correlated with oocyte fertilization potential. However, GJA1, PRSS35, PTX3, and SERPINE2 may not be considered as marker genes for predicting embryo morphology.

Gui LM, Joyce IM. RNA interference evidence that growth differentiation factor-9 mediates oocyte regulation of cumulus expansion in mice. Biol Reprod. 2005;72:195–9.CrossRefPubMed

Su YQ, Wu X, O’Brien MJ, Pendola FL, Denegre JN, Matzuk MM, et al. Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: genetic evidence for an oocyte-granulosa cell regulatory loop. Dev Biol. 2004;276:64–73.CrossRefPubMed

Yokoo M, Sato E. Cumulus-oocyte complex interactions during oocyte maturation. Int Rev Cytol. 2004;235:251–91.CrossRefPubMed

Salustri A, Garlanda C, Hirsch E, De Acetis M, Maccagno A, Bottazzi B, et al. PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization. Development. 2004;131:1577–86.CrossRefPubMed

Varani S, Elvin JA, Yan C, DeMayo J, DeMayo FJ, Horton HF, et al. Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol. 2002;16:1154–67.CrossRefPubMed

Kidder GM, Mhawi AA. Gap junctions and ovarian folliculogenesis. Reproduction. 2002;123:613–20.CrossRefPubMed

Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. Reproduction. 2001;122:829–38.CrossRefPubMed

Matzuk MM, Burns KH, Viveiros MM, Eppig JJ. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science. 2002;296:2178–80.CrossRefPubMed

Assou S, Haouzi D, Mahmoud K, Aouacheria A, Guillemin Y, Pantesco V, et al. A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study. Mol Hum Reprod. 2008;14:711–9.CrossRefPubMed

10.

Cillo F, Brevini TA, Antonini S, Paffoni A, Ragni G, Gandolfi F. Association between human oocyte developmental competence and expression levels of some cumulus genes. Reproduction. 2007;134:645–50.CrossRefPubMed

11.

McKenzie LJ, Pangas SA, Carson SA, Kovanci E, Cisneros P, Buster JE, et al. Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. Hum Reprod. 2004;19:2869–74.CrossRefPubMed

12.

Feuerstein P, Cadoret V, Dalbies-Tran R, Guerif F, Bidault R, Royere D. Gene expression in human cumulus cells: one approach to oocyte competence. Hum Reprod. 2007;22:3069–77.CrossRefPubMed

13.

van Montfoort AP, Geraedts JP, Dumoulin JC, Stassen AP, Evers JL, Ayoubi TA. Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis. Mol Hum Reprod. 2008;14:157–68.CrossRefPubMed

14.

Zhang X, Jafari N, Barnes RB, Confino E, Milad M, Kazer RR. Studies of gene expression in human cumulus cells indicate pentraxin 3 as a possible marker for oocyte quality. Fertil Steril. 2005;83 Suppl 1:1169–79.CrossRefPubMed

15.

Anderson RA, Sciorio R, Kinnell H, Bayne RA, Thong KJ, de Sousa PA, et al. Cumulus gene expression as a predictor of human oocyte fertilisation, embryo development and competence to establish a pregnancy. Reproduction. 2009;138:629–37.CrossRefPubMed

16.

Hasegawa J, Yanaihara A, Iwasaki S, Mitsukawa K, Negishi M, Okai T. Reduction of connexin 43 in human cumulus cells yields good embryo competence during ICSI. J Assist Reprod Genet. 2007;24:463–6.PubMedCentralCrossRefPubMed

17.

Wang HX, Tong D, El-Gehani F, Tekpetey FR, Kidder GM. Connexin expression and gap junctional coupling in human cumulus cells: contribution to embryo quality. J Cell Mol Med. 2009;13:972–84.PubMedCentralCrossRefPubMed

18.

Hamel M, Dufort I, Robert C, Gravel C, Leveille MC, Leader A, et al. Identification of differentially expressed markers in human follicular cells associated with competent oocytes. Hum Reprod. 2008;23:1118–27.CrossRefPubMed

19.

Hamel M, Dufort I, Robert C, Leveille MC, Leader A, Sirard MA. Genomic assessment of follicular marker genes as pregnancy predictors for human IVF. Mol Hum Reprod. 2010;16:87–96.CrossRefPubMed

20.

Gebhardt KM, Feil DK, Dunning KR, Lane M, Russell DL. Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer. Fertil Steril. 2011;96:47–52. e42.CrossRefPubMed

21.

Carabatsos MJ, Sellitto C, Goodenough DA, Albertini DF. Oocyte-granulosa cell heterologous gap junctions are required for the coordination of nuclear and cytoplasmic meiotic competence. Dev Biol. 2000;226:167–79.CrossRefPubMed

22.

Simon AM, Goodenough DA, Li E, Paul DL. Female infertility in mice lacking connexin 37. Nature. 1997;385:525–9.CrossRefPubMed

23.

Li TY, Colley D, Barr KJ, Yee SP, Kidder GM. Rescue of oogenesis in Cx37-null mutant mice by oocyte-specific replacement with Cx43. J Cell Sci. 2007;120:4117–25.CrossRefPubMed

24.

Devjak R, Fon Tacer K, Juvan P, Virant Klun I, Rozman D, Vrtacnik Bokal E. Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist. PLoS One. 2012;7:e47106.PubMedCentralCrossRefPubMed

25.

Lu CH, Lee RK, Hwu YM, Lin MH, Yeh LY, Chen YJ, et al. Involvement of the serine protease inhibitor, SERPINE2, and the urokinase plasminogen activator in cumulus expansion and oocyte maturation. PLoS One. 2013;8:e74602.PubMedCentralCrossRefPubMed

26.

Wahlberg P, Nylander A, Ahlskog N, Liu K, Ny T. Expression and localization of the serine proteases high-temperature requirement factor A1, serine protease 23, and serine protease 35 in the mouse ovary. Endocrinology. 2008;149:5070–7.CrossRefPubMed

27.

Yang WJ, Hwu YM, Lee RK, Li SH, Fleming S. Early-cleavage is a reliable predictor for embryo implantation in the GnRH agonist protocols but not in the GnRH antagonist protocols. Reprod Biol Endocrinol. 2009;7:20.PubMedCentralCrossRefPubMed

28.

Scholtes MC, Zeilmaker GH. A prospective, randomized study of embryo transfer results after 3 or 5 days of embryo culture in in vitro fertilization. Fertil Steril. 1996;65:1245–8.PubMed

29.

Veeck LL. Preembryo grading and degree of cytoplasmic fragmentation. In: Veeck LL, editor. An Atlas of Human Gametes and Conceptuses: An Illustrated Reference for Assisted Reproductive Technology. New York: Parthenon; 1999. p. 46–51.CrossRef

30.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001;25:402–8.CrossRefPubMed

31.

Ekart J, McNatty K, Hutton J, Pitman J. Ranking and selection of MII oocytes in human ICSI cycles using gene expression levels from associated cumulus cells. Hum Reprod. 2013;28:2930–42.CrossRefPubMed

32.

Edry I, Sela-Abramovich S, Dekel N. Meiotic arrest of oocytes depends on cell-to-cell communication in the ovarian follicle. Mol Cell Endocrinol. 2006;252:102–6.CrossRefPubMed

33.

Diao H, Xiao S, Li R, Zhao F, Ye X. Distinct spatiotemporal expression of serine proteases Prss23 and Prss35 in periimplantation mouse uterus and dispensable function of Prss35 in fertility. PLoS One. 2013;8:e56757.PubMedCentralCrossRefPubMed

34.

Leonardsson G, Peng XR, Liu K, Nordstrom L, Carmeliet P, Mulligan R, et al. Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: functional redundancy among physiological plasminogen activators. Proc Natl Acad Sci U S A. 1995;92:12446–50.PubMedCentralCrossRefPubMed

35.

Loutradis D, Drakakis P, Kallianidis K, Milingos S, Dendrinos S, Michalas S. Oocyte morphology correlates with embryo quality and pregnancy rate after intracytoplasmic sperm injection. Fertil Steril. 1999;72:240–4.CrossRefPubMed

36.

Feuerstein P, Puard V, Chevalier C, Teusan R, Cadoret V, Guerif F, et al. Genomic assessment of human cumulus cell marker genes as predictors of oocyte developmental competence: impact of various experimental factors. PLoS One. 2012;7:e40449.PubMedCentralCrossRefPubMed

37.

Wathlet S, Adriaenssens T, Segers I, Verheyen G, Janssens R, Coucke W, et al. New candidate genes to predict pregnancy outcome in single embryo transfer cycles when using cumulus cell gene expression. Fertil Steril. 2012;98:432–9. e431-434.CrossRefPubMed

38.

Wathlet S, Adriaenssens T, Segers I, Verheyen G, Van Landuyt L, Coucke W, et al. Pregnancy prediction in single embryo transfer cycles after ICSI using QPCR: validation in oocytes from the same cohort. PLoS One. 2013;8:e54226.PubMedCentralCrossRefPubMed

39.

Burnik Papler T, Vrtacnik Bokal E, Maver A, Lovrecic L. Specific gene expression differences in cumulus cells as potential biomarkers of pregnancy. Reprod Biomed Online. 2015;30:426–33.CrossRefPubMed

Title: Correlation of cumulus gene expression of GJA1, PRSS35, PTX3, and SERPINE2 with oocyte maturation, fertilization, and embryo development
Authors: Sheng-Hsiang Li
Ming-Huei Lin
Yuh-Ming Hwu
Chung-Hao Lu
Ling-Yu Yeh
Ying-Jie Chen
Robert Kuo-Kuang Lee
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Reproductive Biology and Endocrinology / Issue 1/2015
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/s12958-015-0091-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Correlation of cumulus gene expression of GJA1, PRSS35, PTX3, and SERPINE2 with oocyte maturation, fertilization, and embryo development

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2015

Predictive factors for ovarian response in a corifollitropin alfa/GnRH antagonist protocol for controlled ovarian stimulation in IVF/ICSI cycles

Is there an androgen level threshold for aneuploidy risk in infertile women?

Nuclear factor of activated T-cell isoform expression and regulation in human myometrium

Reproducibility and clinical significance of pre-ovulatory serum progesterone level and progesterone/estradiol ratio on the day of human chorionic gonadotropin administration in infertile women undergoing repeated in vitro fertilization cycles

Gestation-specific reference intervals for comprehensive spot urinary steroid hormone metabolite analysis in normal singleton pregnancy and 6 weeks postpartum

Human sperm degradation of zona pellucida proteins contributes to fertilization