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Published in: Reproductive Biology and Endocrinology 1/2012

Open Access 01-12-2012 | Research

Detection of RUNX2 gene expression in cumulus cells in women undergoing controlled ovarian stimulation

Authors: Myrto Papamentzelopoulou, Despina Mavrogianni, Vasiliki Dinopoulou, Haralampos Theofanakis, Fotodotis Malamas, Spyros Marinopoulos, Ritsa Bletsa, Elli Anagnostou, Kostas Kallianidis, Dimitris Loutradis

Published in: Reproductive Biology and Endocrinology | Issue 1/2012

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Abstract

Background

RUNX2 is a transcription factor, whose expression has been recently identified in the mouse ovary. Regulation of RUNX2 expression and its function in the human ovary have not been determined yet. The aim of the present study is the investigation of the possible correlation between RUNX2 gene expression in cumulus cells and controlled ovarian stimulation and pregnancy outcomes after ART treatment.

Methods

A total of 41 patients undergoing ICSI treatment for male factor infertility were enrolled into a specific ART program, during which cumulus cells were collected. The expression of RUNX2 gene in cumulus cells was examined by real-time PCR.

Results

Concerning RUNX2 gene expression, 12 out of 41 women were detected with RUNX2 expression, with ratios ranging from 0.84 to 1.00, while 28 out of 41 women had no expression (ratio = 0). Only 1 woman presented a weak RUNX2 gene expression (ratio = 0.52). From 8 women that proceeded to pregnancy, 7 of them did not express RUNX2 gene in cumulus cells, while one was the woman with weak gene expression that also achieved pregnancy. The group of women without RUNX2 expression presented higher number of follicles (p = 0.013), higher number of retrieved oocytes (p = 0.016), higher basal LH serum levels (p = 0.016) and higher peak estradiol levels (p = 0.013), while the number of fertilized oocytes differed marginally between the two groups (p = 0.089). Moreover, RUNX2 expression was negatively associated with LH levels (OR = 0.22, p = 0.021) and E2 levels (OR = 0.25, p = 0.026).

Conclusions

Consequently, based on the preliminary findings of the present pilot study a potential inhibitory mechanism of RUNX2 gene is observed in the ovary when high mRNA levels are detected, suggesting that RUNX2 could possibly be used as a candidate genetic marker in the monitoring of the outcome of an ART treatment.
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Literature
1.
go back to reference Devroey P, Fauser BCJM, Diedrich K: Approaches to improve the diagnosis and management of infertility. Hum Reprod Update. 2009, 15 (4): 391-408. 10.1093/humupd/dmp012.PubMedCentralCrossRefPubMed Devroey P, Fauser BCJM, Diedrich K: Approaches to improve the diagnosis and management of infertility. Hum Reprod Update. 2009, 15 (4): 391-408. 10.1093/humupd/dmp012.PubMedCentralCrossRefPubMed
2.
go back to reference Stock M, Schafer H, Fliegauf M, Otto F: Identification of novel target genes of the bone-specific transcription factor RUNX2. J Bone Miner Res. 2004, 19: 959-972. 10.1359/jbmr.2004.19.6.959.CrossRefPubMed Stock M, Schafer H, Fliegauf M, Otto F: Identification of novel target genes of the bone-specific transcription factor RUNX2. J Bone Miner Res. 2004, 19: 959-972. 10.1359/jbmr.2004.19.6.959.CrossRefPubMed
3.
go back to reference Wang GX, Sun RP, Song FL: A novel RUNX2 mutation (T420I) in Chinese patients with cleidocranial dysplasia. Genet Mol Res. 2010, 9 (1): 41-47. 10.4238/vol9-1gmr685.CrossRefPubMed Wang GX, Sun RP, Song FL: A novel RUNX2 mutation (T420I) in Chinese patients with cleidocranial dysplasia. Genet Mol Res. 2010, 9 (1): 41-47. 10.4238/vol9-1gmr685.CrossRefPubMed
4.
go back to reference Lou Y, Javed A, Hussain S, Colby J, Frederick D, Pratap J, Xie R, Gaur T, Wijnen AJ, Jones SN, et al: A RUNX2 threshold for the cleidocranial dysplasia phenotype. Hum Mol Genet. 2009, 18 (3): 556-568.PubMedCentralCrossRefPubMed Lou Y, Javed A, Hussain S, Colby J, Frederick D, Pratap J, Xie R, Gaur T, Wijnen AJ, Jones SN, et al: A RUNX2 threshold for the cleidocranial dysplasia phenotype. Hum Mol Genet. 2009, 18 (3): 556-568.PubMedCentralCrossRefPubMed
5.
go back to reference Hernandez-Gonzalez I, Gonzalez-Robayna I, Shimada M, Wayne CM, Ochsner SA, White L, Richards JS: Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes: does this expand their role in the ovulation process?. Mol Endocrinol. 2006, 20 (6): 1300-1321.CrossRefPubMed Hernandez-Gonzalez I, Gonzalez-Robayna I, Shimada M, Wayne CM, Ochsner SA, White L, Richards JS: Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes: does this expand their role in the ovulation process?. Mol Endocrinol. 2006, 20 (6): 1300-1321.CrossRefPubMed
6.
go back to reference Park ES, Choi S, Lind AK, Dahm-Kahler P, Brannstrom M, Carletti M, Christenson KL, Curry TE, Jo M: The LH surge-induced RUNX2 transcription factor regulates the expression of specific genes in luteinizing granulosa cells. Biol Reprod. 2009, 81: 357- Park ES, Choi S, Lind AK, Dahm-Kahler P, Brannstrom M, Carletti M, Christenson KL, Curry TE, Jo M: The LH surge-induced RUNX2 transcription factor regulates the expression of specific genes in luteinizing granulosa cells. Biol Reprod. 2009, 81: 357-
7.
go back to reference He N, Xiao Z, Yin T, Stubbs J, Li L, Quarles LD: Inducible expression of RUNX2 results in multiorgan abnormalities in mice. J Cell Biochem. 2011, 112 (2): 653-665. 10.1002/jcb.22968.CrossRefPubMed He N, Xiao Z, Yin T, Stubbs J, Li L, Quarles LD: Inducible expression of RUNX2 results in multiorgan abnormalities in mice. J Cell Biochem. 2011, 112 (2): 653-665. 10.1002/jcb.22968.CrossRefPubMed
8.
go back to reference Fan HY, Liu Z, Johnson PF, Richards JS: CCAAT/enhancer-binding proteins (C/EBP)-α and -β are essential for ovulation, luteinization, and the expression of key target genes. Mol Endocrinol. 2011, 25 (2): 253-268. 10.1210/me.2010-0318.PubMedCentralCrossRefPubMed Fan HY, Liu Z, Johnson PF, Richards JS: CCAAT/enhancer-binding proteins (C/EBP)-α and -β are essential for ovulation, luteinization, and the expression of key target genes. Mol Endocrinol. 2011, 25 (2): 253-268. 10.1210/me.2010-0318.PubMedCentralCrossRefPubMed
9.
go back to reference Alarcón-Riquelme ME: Role of RUNX in autoimmune diseases linking rheumatoid arthritis, psoriasis and lupus. Arthritis Res Ther. 2004, 6: 169-173. 10.1186/ar1203.PubMedCentralCrossRefPubMed Alarcón-Riquelme ME: Role of RUNX in autoimmune diseases linking rheumatoid arthritis, psoriasis and lupus. Arthritis Res Ther. 2004, 6: 169-173. 10.1186/ar1203.PubMedCentralCrossRefPubMed
10.
go back to reference McCarthy TL, Chang WZ, Liu Y, Centrella M: RUNX2 integrates estrogen activity in osteoblasts. J Biol Chem. 2003, 278 (44): 43121-43129. 10.1074/jbc.M306531200.CrossRefPubMed McCarthy TL, Chang WZ, Liu Y, Centrella M: RUNX2 integrates estrogen activity in osteoblasts. J Biol Chem. 2003, 278 (44): 43121-43129. 10.1074/jbc.M306531200.CrossRefPubMed
11.
go back to reference Jeong JH, Jung JK, Kim HJ, Jin JS, Kim HN, Kang SM, Kim SY, Wijnen AJ, Stein JL, Lian JB, et al: The gene for aromatase, a rate-limiting enzyme for local estrogen biosynthesis, is a downstream target gene of RUNX2 in skeletal tissues. Mol Cell Biol. 2010, 30 (10): 2365-2375. 10.1128/MCB.00672-09.PubMedCentralCrossRefPubMed Jeong JH, Jung JK, Kim HJ, Jin JS, Kim HN, Kang SM, Kim SY, Wijnen AJ, Stein JL, Lian JB, et al: The gene for aromatase, a rate-limiting enzyme for local estrogen biosynthesis, is a downstream target gene of RUNX2 in skeletal tissues. Mol Cell Biol. 2010, 30 (10): 2365-2375. 10.1128/MCB.00672-09.PubMedCentralCrossRefPubMed
12.
go back to reference Park ES, Lind AK, Dahm-Kähler P, Brännström M, Carletti MZ, Christenson LK, Curry TE, Jo M: RUNX2 transcription factor regulates gene expression in luteinizing granulosa cells of rat ovaries. Mol Endocrinol. 2010, 24 (4): 846-858. 10.1210/me.2009-0392.PubMedCentralCrossRefPubMed Park ES, Lind AK, Dahm-Kähler P, Brännström M, Carletti MZ, Christenson LK, Curry TE, Jo M: RUNX2 transcription factor regulates gene expression in luteinizing granulosa cells of rat ovaries. Mol Endocrinol. 2010, 24 (4): 846-858. 10.1210/me.2009-0392.PubMedCentralCrossRefPubMed
13.
go back to reference Palermo G, Joris H, Devroey P, Van Steirteghem AC: Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992, 340 (8810): 17-18. 10.1016/0140-6736(92)92425-F.CrossRefPubMed Palermo G, Joris H, Devroey P, Van Steirteghem AC: Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992, 340 (8810): 17-18. 10.1016/0140-6736(92)92425-F.CrossRefPubMed
14.
go back to reference Patsoula E, Loutradis D, Drakakis P, Michalas L, Bletsa R, Michalas S: Messenger RNA expression for the follicle-stimulating hormone receptor and luteinizing hormone receptor in human oocytes and preimplantation-stage embryos. Fertil Steril. 2003, 79 (5): 1187-1193. 10.1016/S0015-0282(03)00071-2.CrossRefPubMed Patsoula E, Loutradis D, Drakakis P, Michalas L, Bletsa R, Michalas S: Messenger RNA expression for the follicle-stimulating hormone receptor and luteinizing hormone receptor in human oocytes and preimplantation-stage embryos. Fertil Steril. 2003, 79 (5): 1187-1193. 10.1016/S0015-0282(03)00071-2.CrossRefPubMed
15.
go back to reference Müller MC, Saglio G, Lin F, Pfeifer H, Press RD, Tubbs RR, Paschka P, Gottardi E, O’Brien SG, Ottmann OG, et al: An international study to standardize the detection and quantitation of BCR-ABL transcripts from stabilized peripheral blood preparations by quantitative RT-PCR. Haematologica. 2007, 92: 970-973. 10.3324/haematol.11172.CrossRefPubMed Müller MC, Saglio G, Lin F, Pfeifer H, Press RD, Tubbs RR, Paschka P, Gottardi E, O’Brien SG, Ottmann OG, et al: An international study to standardize the detection and quantitation of BCR-ABL transcripts from stabilized peripheral blood preparations by quantitative RT-PCR. Haematologica. 2007, 92: 970-973. 10.3324/haematol.11172.CrossRefPubMed
16.
go back to reference Choi S, Park ES, Jo M: The expression pattern of core binding factor during the periovulatory period in the rat ovary. Biol Reprod. 2007, 77: 97-c–98. Choi S, Park ES, Jo M: The expression pattern of core binding factor during the periovulatory period in the rat ovary. Biol Reprod. 2007, 77: 97-c–98.
17.
go back to reference Park ES, Park J, Franceschi RT, Jo M: The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells. Mol Cell Endocrinol. 2012, 362 (1–2): 165-175.CrossRefPubMed Park ES, Park J, Franceschi RT, Jo M: The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells. Mol Cell Endocrinol. 2012, 362 (1–2): 165-175.CrossRefPubMed
18.
go back to reference Liu J, Park ES, Curry TE, Jo M: Periovulatory expression of hyaluronan and proteoglycan link protein 1 (Hapln1) in the rat ovary: hormonal regulation and potential function. Mol Endocrinol. 2010, 24: 1203-1217. 10.1210/me.2009-0325.PubMedCentralCrossRefPubMed Liu J, Park ES, Curry TE, Jo M: Periovulatory expression of hyaluronan and proteoglycan link protein 1 (Hapln1) in the rat ovary: hormonal regulation and potential function. Mol Endocrinol. 2010, 24: 1203-1217. 10.1210/me.2009-0325.PubMedCentralCrossRefPubMed
19.
go back to reference Sun GW, Kobayashi H, Suzuki M, Kanayama N, Terao T: Link protein as an enhancer of cumulus cell-oocyte complex expansion. Mol Reprod Dev. 2002, 63: 223-231. 10.1002/mrd.90008.CrossRefPubMed Sun GW, Kobayashi H, Suzuki M, Kanayama N, Terao T: Link protein as an enhancer of cumulus cell-oocyte complex expansion. Mol Reprod Dev. 2002, 63: 223-231. 10.1002/mrd.90008.CrossRefPubMed
20.
go back to reference 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 (2): 240-244. 10.1016/S0015-0282(99)00233-2.CrossRefPubMed 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 (2): 240-244. 10.1016/S0015-0282(99)00233-2.CrossRefPubMed
21.
go back to reference Khalid O, Baniwal SK, Purcell DJ, Leclerc N, Gabet Y, Stallcup MR, Coetzee GA, Frenkel B: Modulation of RUNX2 activity by estrogen receptor-alpha: implications for osteoporosis and breast cancer. Endocrinology. 2008, 149 (12): 5984-5995. 10.1210/en.2008-0680.PubMedCentralCrossRefPubMed Khalid O, Baniwal SK, Purcell DJ, Leclerc N, Gabet Y, Stallcup MR, Coetzee GA, Frenkel B: Modulation of RUNX2 activity by estrogen receptor-alpha: implications for osteoporosis and breast cancer. Endocrinology. 2008, 149 (12): 5984-5995. 10.1210/en.2008-0680.PubMedCentralCrossRefPubMed
22.
go back to reference Chimge NO, Baniwal SK, Little GH, Chen YB, Kahn M, Tripathy D, Borok Z, Frenkel B: Regulation of breast cancer metastasis by Runx2 and estrogen signaling: the role of SNAI2. Breast Cancer Res. 2011, 13 (6): R127-10.1186/bcr3073.PubMedCentralCrossRefPubMed Chimge NO, Baniwal SK, Little GH, Chen YB, Kahn M, Tripathy D, Borok Z, Frenkel B: Regulation of breast cancer metastasis by Runx2 and estrogen signaling: the role of SNAI2. Breast Cancer Res. 2011, 13 (6): R127-10.1186/bcr3073.PubMedCentralCrossRefPubMed
23.
go back to reference Chimge NO, Baniwal SK, Luo J, Coetzee S, Khalid O, Berman BP, Tripathy D, Ellis MJ, Frenkel B: Opposing effects of Runx2 and estradiol on breast cancer cell proliferation: in vitro identification of reciprocally regulated gene signature related to clinical letrozole responsiveness. Clin Cancer Res. 2012, 18 (3): 901-911. 10.1158/1078-0432.CCR-11-1530.PubMedCentralCrossRefPubMed Chimge NO, Baniwal SK, Luo J, Coetzee S, Khalid O, Berman BP, Tripathy D, Ellis MJ, Frenkel B: Opposing effects of Runx2 and estradiol on breast cancer cell proliferation: in vitro identification of reciprocally regulated gene signature related to clinical letrozole responsiveness. Clin Cancer Res. 2012, 18 (3): 901-911. 10.1158/1078-0432.CCR-11-1530.PubMedCentralCrossRefPubMed
Metadata
Title
Detection of RUNX2 gene expression in cumulus cells in women undergoing controlled ovarian stimulation
Authors
Myrto Papamentzelopoulou
Despina Mavrogianni
Vasiliki Dinopoulou
Haralampos Theofanakis
Fotodotis Malamas
Spyros Marinopoulos
Ritsa Bletsa
Elli Anagnostou
Kostas Kallianidis
Dimitris Loutradis
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2012
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-10-99

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