nach oben

Journal of Assisted Reproduction and Genetics

Erschienen in:

01.10.2013 | Assisted Reproduction Technologies

Notch signaling pathway in cumulus cells can be a novel marker to identify poor and normal responder IVF patients

verfasst von: Gamze Tanriverdi, Secnur Denir, Sule Ayla, Ayhan Bilir, Huseyin Oktar, Ismail Cepni, Tulay Irez

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 10/2013

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To identify expression of Notch signaling proteins and its ligands in human cumulus cells which were obtained by follicle aspiration and to compare the differences of this protein expression between the normal and poor responder patients.

Methods

47 patients who applied to the assisted reproductive treatments with various infertility problems were included to the study. Controlled ovarian hyperstimulation was performed by using GnRH agonist and gonadotropins. Serum hormon levels were measured by using Chemilluminescent Microparticle Immunoassay method for each patient. After ultrasonographic ovarian follicle screening, oocytes were retrievaled. Cumulus cells obtained from the follicles were cultured for 72 h and immunuhistochemistry were performed for Notch1, Notch2, Notch3, Notch4, Jagged1 and Jagged2 proteins. Histological score (HSCORE) were applied to all of the samples. The association between Notch and its ligands protein expressions and the oocyte-embryo quality and fertilization rates were investigated.

Results

Significant differences were observed between the mean values of age, AMH and FSH in the 2 groups, respectively (p < 0.05). However, the mean female infertility duration and total gonadotropin dose did not differ significantly between normal and poor responder groups. All the patients cumulus cells expressed Notch1, Notch2, Notch3, Notch4, Jagged1 and Jagged2. There was a significant difference (p < 0.05) only for Notch2 between the 2 groups and a positive correlation between Notch2 and Notch3 (r = 547, p = 0.00) expressions were noted. Furthermore, no correlations were observed between the following: Notch1, Notch2, Notch3, Notch4, Jagged1, and Jagged2 expression; mature oocyte number; fertilization rates, and embryo quality percentage in both of the groups.

Conclusion

Notch signalling proteins can be an indicator for understanding the ovarian response in ovulation induction.

Johnson J, Espinoza T, McGaughey RW, Rawls A, Wilson-Rawls J. Notch pathway genes are expressed in mammalian ovarian follicles. Mech Dev. 2001;109(2):355–61.PubMedCrossRef

Knight PG, Glister C. TGF-beta superfamily members and ovarian follicle development. Reproduction. 2006;132:191–206.PubMedCrossRef

Russell DL, Robker RL. Molecular mechanisms of ovulation: co-ordination through the cumulus complex. Hum Reprod Updat. 2007;13:289–312.CrossRef

Uyar A, Torrealday S, Seli E. Cumulus and granulosa cell markers of oocyte and embryo quality. Fertil Steril. 2013;99(4):979–97.PubMedCrossRef

Teilmann SC. Differential expression and localisation of connexin-37 and connexin-43 in follicles of different stages in the 4-week-old mouse ovary. MolCell Endocrinol. 2005;234:27–35.CrossRef

Trombly DJ, Woodruff TK, Mayo KE. Suppression of Notch signaling in the neonatal mouse ovary decreases primordial follicle formation. Endocrinology. 2009;150:1014–24.PubMedCrossRefPubMedCentral

Wang Z, Li Y, Banerjee S, Sarkar FH. Exploitation of the Notch signaling pathway as a novel target for cancer therapy. Anticancer Res. 2008;28:3621–30.PubMed

Cepni I, Kahraman N, Ocal P, Idil M, Uludag S. Expression and comparison of gap junction protein connexin 37 in granulosa cells aspirates from follicles of poor responder and nonpoor responder patients. Fertil Steril. 2008;89:417–20.PubMedCrossRef

Veeck LL. Oocyte assesment and biological performance. Ann N Y Acad Sci. 1999;541:259–74.CrossRef

10.

Ocal P, Ersoylu B, Cepni I, Guralp O, Atakul N, Irez T, et al. The association between homocysteine in the follicular fluid with embryo quality and pregnancy rate in assisted reproductive techniques. J Assist Reprod Genet. 2012;29:299–304.PubMedCrossRefPubMedCentral

11.

Idil M, Cepni I, Demirsoy G, Ocal P, Salihoğlu F, Senol H, et al. Does granulosa cell apoptosis have a role in the etiology of unexplained infertility? Eur J Obstet Gynecol Reprod Biol. 2004;112:182–4.PubMedCrossRef

12.

Jancar N, Kopitar AN, Ihan A, Virant Klun I, Bokal EV. Effect of apoptosis and reactive oxygen species production in human granulosa cells on oocyte fertilization and blastocyst development. J Assist Reprod Genet. 2007;24:91–7.PubMedCrossRefPubMedCentral

13.

Tingen C, Kim A, Woodruff TK. The primordial pool of follicles and nest breakdown in mammalian ovaries. Mol Hum Reprod. 2009;15:795–803.PubMedCrossRefPubMedCentral

14.

Otsuka F, McTavish KJ, Shimasaki S. Integral role of GDF-9 and BMP-15 in ovarian function. Mol Reprod Dev. 2011;78(1):9–21. doi:10.1002/mrd.21265. Epub 2011 Jan 11. PubMed PMID: 21226076; PubMed Central PMCID: PMC3051839.PubMedCrossRefPubMedCentral

15.

Edson MA, Nalam RL, Clementi C, Franco HL, Demayo FJ, Lyons KM, et al. Granulosa cell-expressed BMPR1A and BMPR1B have unique functions in regulating fertility but act redundantly to suppress ovarian tumor development. Mol Endocrinol. 2010;24:1251–66.PubMedCrossRefPubMedCentral

16.

Vorontchikhina MA, Zimmermann RC, Shawber CJ, Tang H, Kitajewski J. Unique patterns of Notch1, Notch4 and Jagged1 expression in ovarian vessels during folliculogenesis and corpus luteum formation. Gene Expr Patterns. 2005;5:701–9.PubMedCrossRef

17.

Jiang R, Lan Y, Chapman HD, Shawber C, Norton CR, Serreze DV, et al. Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice. Genes Dev. 1998;12:1046–57.PubMedCrossRefPubMedCentral

18.

Krebs LT, Xue Y, Norton CR, Sundberg JP, Beatus P, Lendahl U, et al. Characterization of Notch3-deficient mice: normal embryonic development and absence of genetic interactions with a Notch1 mutation. Genesis. 2003;37(3):139–43. PubMed PMID: 14595837.PubMedCrossRef

19.

Krebs LT, Xue Y, Norton CR, Shutter JR, Maguire M, Sundberg JP, et al. Notch signaling is essential for vascular morphogenesis in mice. Genes Dev. 2000;14:1343–52.PubMedPubMedCentral

20.

Guo S, Liu M, Gonzalez-Perez RR. Role of Notch and its oncogenic signaling crosstalk in breast cancer. Biochim Biophys Acta. 1815;2011:197–213.

21.

Feyles V, Gianetto-Berruti A. Poor responders in assisted reproduction cycles. Minerva Ginecol. 2005;57:1–14.PubMed

22.

Pellicer A, Ardiles G, Neuspiller F, Remohi J, Simon C, Bonilla-Musoles F. Evaluation of the ovarian reserve in young low responders with normal basallevels of follicle-stimulating hormone using three-dimensional ultrasonography. Fertil Steril. 1998;70(4):671–5.PubMedCrossRef

23.

Faber BM, Mayer J, Cox B, Jones D, Toner JP, Oehninger S, et al. Cessation of gonadotropin-releasing hormone agonist therapy combined with high-dose gonadotropin stimulation yields favorable pregnancy results in low responders. Fertil Steril. 1998;69(5):826–30.PubMedCrossRef

24.

Karande V, Gleicher N. A rational approach to the management of low responders in in-vitro fertilization. Hum Reprod. 1999;14:1744–8.PubMedCrossRef

25.

Vollenhoven B, Osianlis T, Catt J. Is there an ideal stimulation regimen for IVF for poor responders and does it change with age? J Assist Reprod Genet. 2008;25:523–9.PubMedCrossRefPubMedCentral

26.

Seifer DB, Gardiner AC, Ferreira KA, Peluso JJ. Apoptosis as a function of ovarian reserve in women undergoing in vitro fertilization. Fertil Steril. 1996;66:593–8.PubMed

27.

Xue Y, Gao X, Lindsell CE, Norton CR, Chang B, Hicks C, et al. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1. Hum Mol Genet. 1999;8(5):723–30.PubMedCrossRef

28.

Hamada Y, Kadokawa Y, Okabe M, Ikawa M, Coleman JR, Tsujimoto Y. Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality. Development. 1999;126(15):3415–24.PubMed

29.

Jovanovic VP, Sauer CM, Shawber CJ, Gomez R, Wang X, Sauer MV, et al. Intraovarian regulation of gonadotropin-dependent folliculogenesis depends on notch receptor signaling pathways not involving Delta-like ligand 4 (Dll4). Reprod Biol Endocrinol. 2013;11:43.PubMedCrossRefPubMedCentral

30.

Visser JA, de Jong FH, Laven JS, Themmen AP. Anti-Müllerian hormone: a new marker for ovarian function. Reproduction. 2006;131(1):1–9.PubMedCrossRef

31.

Choi MH, Yoo JH, Kim HO, Cha SH, Park CW, Yang KM, et al. Serum anti-Müllerian hormone levels as a predictor of the ovarian response and IVF outcomes. Clin Exp Reprod Med. 2011;38:153–8.PubMedCrossRefPubMedCentral

Titel: Notch signaling pathway in cumulus cells can be a novel marker to identify poor and normal responder IVF patients
verfasst von: Gamze Tanriverdi
Secnur Denir
Sule Ayla
Ayhan Bilir
Huseyin Oktar
Ismail Cepni
Tulay Irez
Publikationsdatum: 01.10.2013
Verlag: Springer US
Erschienen in: Journal of Assisted Reproduction and Genetics / Ausgabe 10/2013
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-013-0072-4

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen

Springer Medizin

Notch signaling pathway in cumulus cells can be a novel marker to identify poor and normal responder IVF patients