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Published in: Reproductive Biology and Endocrinology 1/2012

Open Access 01-12-2012 | Research

Expression of HOXA11 in the mid-luteal endometrium from women with endometriosis-associated infertility

Authors: Malgorzata Szczepańska, Przemyslaw Wirstlein, Jana Skrzypczak, Paweł P Jagodziński

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

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Abstract

Background

A decrease in HOXA11 expression in eutopic mid-secretory endometrium has been found in women with endometriosis-associated infertility.

Methods

Using Real-time quantitative PCR (RQ-PCR) and western blotting analysis we studied the HOXA11 transcript and protein levels in mid-luteal eutopic endometrium from eighteen infertile women with minimal endometriosis, sixteen healthy fertile women and sixteen infertile women with fallopian tubal occlusion from the Polish population. We also evaluated transcript levels of DNA methyltransferases DNMT1, DNMT3A and DNMT3B in these groups of women.

Results

There were significantly lower levels of HOXA11 transcripts (p = 0.003, p = 0.041) and protein (p = 0.004, p = 0.001) in women with endometriosis as compared to fertile women and infertile women with tubal occlusion. Moreover, we found significantly higher methylation levels of the CpG region in the first exon of HOXA11 in infertile women with endometriosis compared with fertile women (p < 0.001) and infertile women with tubal occlusion (p < 0.001). We also observed significantly increased levels of DNMT3A transcript in women with endometriosis than fertile women (p = 0.044) and infertile women with tubal occlusion (p = 0.047). However, we did not observe significant differences in DNMT1 and DNMT3B transcript levels between these investigated groups of women.

Conclusions

We confirmed that reduced HOXA11 expression may contribute to endometriosis-associated infertility. Moreover, we found that DNA hypermethylation can be one of the possible molecular mechanisms causing a decrease in HOXA11 expression in the eutopic mid-secretory endometrium in infertile women with endometriosis.
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Literature
1.
2.
go back to reference Ulukus M, Cakmak H, Arici A: The role of endometrium in endometriosis. J Soc Gynecol Investig. 2006, 13: 467-476.PubMed Ulukus M, Cakmak H, Arici A: The role of endometrium in endometriosis. J Soc Gynecol Investig. 2006, 13: 467-476.PubMed
3.
go back to reference de Ziegler D, Borghese B, Chapron C: Endometriosis and infertility: pathophysiology and management. Lancet. 2010, 376: 730-738. 10.1016/S0140-6736(10)60490-4.CrossRefPubMed de Ziegler D, Borghese B, Chapron C: Endometriosis and infertility: pathophysiology and management. Lancet. 2010, 376: 730-738. 10.1016/S0140-6736(10)60490-4.CrossRefPubMed
4.
go back to reference Houston DE: Evidence for the risk of pelvic endometriosis by age, race and socioeconomic status. Epidemiol Rev. 1984, 6: 167-191.PubMed Houston DE: Evidence for the risk of pelvic endometriosis by age, race and socioeconomic status. Epidemiol Rev. 1984, 6: 167-191.PubMed
5.
go back to reference Strathy JH, Molgaard CA, Coulam CB, Melton LJ: Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril. 1982, 38: 667-672.PubMed Strathy JH, Molgaard CA, Coulam CB, Melton LJ: Endometriosis and infertility: a laparoscopic study of endometriosis among fertile and infertile women. Fertil Steril. 1982, 38: 667-672.PubMed
6.
go back to reference Simón C, Gutiérrez A, Vidal A, de los Santos MJ, Tarín JJ, Remohí J, Pellicer A: Outcome of patients with endometriosis in assisted reproduction: results from in vitro fertilization and oocyte donation. Hum Reprod. 1994, 9: 725-729.PubMed Simón C, Gutiérrez A, Vidal A, de los Santos MJ, Tarín JJ, Remohí J, Pellicer A: Outcome of patients with endometriosis in assisted reproduction: results from in vitro fertilization and oocyte donation. Hum Reprod. 1994, 9: 725-729.PubMed
7.
go back to reference Tummon IS, Maclin VM, Radwanska E, Binor Z, Dmowski WP: Occult ovulatory dysfunction in women with minimal endometriosis or unexplained infertility. Fertil Steril. 1988, 50: 716-720.PubMed Tummon IS, Maclin VM, Radwanska E, Binor Z, Dmowski WP: Occult ovulatory dysfunction in women with minimal endometriosis or unexplained infertility. Fertil Steril. 1988, 50: 716-720.PubMed
8.
go back to reference Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, Osteen K, Taylor RN, Lessey BA, Giudice LC: Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002, 143: 2119-2138. 10.1210/en.143.6.2119.CrossRefPubMed Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, Osteen K, Taylor RN, Lessey BA, Giudice LC: Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002, 143: 2119-2138. 10.1210/en.143.6.2119.CrossRefPubMed
9.
go back to reference Burney RO, Talbi S, Hamilton AE, Vo KC, Nyegaard M, Nezhat CR, Lessey BA, Giudice LC: Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007, 148: 3814-3826. 10.1210/en.2006-1692.CrossRefPubMed Burney RO, Talbi S, Hamilton AE, Vo KC, Nyegaard M, Nezhat CR, Lessey BA, Giudice LC: Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007, 148: 3814-3826. 10.1210/en.2006-1692.CrossRefPubMed
10.
go back to reference Kamat AA, Younes PS, Sayeeduddin M, Wheeler TM, Simpson JL, Agoulnik AI: Protein expression profiling of endometriosis: validation of 2-mm tissue microarrays. Fertil Steril. 2004, 82: 1681-1683. 10.1016/j.fertnstert.2004.06.044.CrossRefPubMed Kamat AA, Younes PS, Sayeeduddin M, Wheeler TM, Simpson JL, Agoulnik AI: Protein expression profiling of endometriosis: validation of 2-mm tissue microarrays. Fertil Steril. 2004, 82: 1681-1683. 10.1016/j.fertnstert.2004.06.044.CrossRefPubMed
11.
go back to reference Kao LC, Germeyer A, Tulac S, Lobo S, Yang JP, Taylor RN, Osteen K, Lessey BA, Giudice LC: Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology. 2003, 144: 2870-28781. 10.1210/en.2003-0043.CrossRefPubMed Kao LC, Germeyer A, Tulac S, Lobo S, Yang JP, Taylor RN, Osteen K, Lessey BA, Giudice LC: Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology. 2003, 144: 2870-28781. 10.1210/en.2003-0043.CrossRefPubMed
12.
go back to reference Gurates B, Bulun SE: Endometriosis: the ultimate hormonal disease. Semin Reprod Med. 2003, 21: 125-134.CrossRefPubMed Gurates B, Bulun SE: Endometriosis: the ultimate hormonal disease. Semin Reprod Med. 2003, 21: 125-134.CrossRefPubMed
13.
go back to reference Paul Dmowski W, Braun DP: Immunology of endometriosis. Best Pract Res Clin Obstet Gynaecol. 2004, 18: 245-263. 10.1016/j.bpobgyn.2004.02.001.CrossRefPubMed Paul Dmowski W, Braun DP: Immunology of endometriosis. Best Pract Res Clin Obstet Gynaecol. 2004, 18: 245-263. 10.1016/j.bpobgyn.2004.02.001.CrossRefPubMed
14.
go back to reference Rier SE: The potential role of exposure to environmental toxicants in the pathophysiology of endometriosis. Ann N Y Acad Sci. 2002, 955: 201-212. 10.1111/j.1749-6632.2002.tb02781.x. discussion 230-2, 396-406CrossRefPubMed Rier SE: The potential role of exposure to environmental toxicants in the pathophysiology of endometriosis. Ann N Y Acad Sci. 2002, 955: 201-212. 10.1111/j.1749-6632.2002.tb02781.x. discussion 230-2, 396-406CrossRefPubMed
15.
go back to reference Barlow DH, Kennedy S: Endometriosis: new genetic approaches and therapy. Annu Rev Med. 2005, 56: 345-356. 10.1146/annurev.med.55.091902.103805.CrossRefPubMed Barlow DH, Kennedy S: Endometriosis: new genetic approaches and therapy. Annu Rev Med. 2005, 56: 345-356. 10.1146/annurev.med.55.091902.103805.CrossRefPubMed
16.
go back to reference Wu Y, Halverson G, Basir Z, Strawn E, Yan P, Guo SW: Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis. Am J Obstet Gynecol. 2005, 193: 371-380. 10.1016/j.ajog.2005.01.034.CrossRefPubMed Wu Y, Halverson G, Basir Z, Strawn E, Yan P, Guo SW: Aberrant methylation at HOXA10 may be responsible for its aberrant expression in the endometrium of patients with endometriosis. Am J Obstet Gynecol. 2005, 193: 371-380. 10.1016/j.ajog.2005.01.034.CrossRefPubMed
17.
go back to reference Wu Y, Strawn E, Basir Z, Halverson G, Guo SW: Promoter hypermethylation of progesterone receptor isoform B (PR-B) in endometriosis. Epigenetics. 2006, 1: 106-111. 10.4161/epi.1.2.2766.CrossRefPubMed Wu Y, Strawn E, Basir Z, Halverson G, Guo SW: Promoter hypermethylation of progesterone receptor isoform B (PR-B) in endometriosis. Epigenetics. 2006, 1: 106-111. 10.4161/epi.1.2.2766.CrossRefPubMed
18.
go back to reference Xue Q, Lin Z, Yin P, Milad MP, Cheng YH, Confino E, Reierstad S, Bulun SE: Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5' CpG island in endometriosis. J Clin Endocrinol Metab. 2007, 92: 3261-3247. 10.1210/jc.2007-0494.CrossRefPubMed Xue Q, Lin Z, Yin P, Milad MP, Cheng YH, Confino E, Reierstad S, Bulun SE: Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5' CpG island in endometriosis. J Clin Endocrinol Metab. 2007, 92: 3261-3247. 10.1210/jc.2007-0494.CrossRefPubMed
19.
go back to reference Xue Q, Lin Z, Cheng YH, Huang CC, Marsh E, Yin P, Milad MP, Confino E, Reierstad S, Innes J, Bulun SE: Promoter methylation regulates estrogen receptor 2 in human endometrium and endometriosis. Biol Reprod. 2007, 77: 681-687. 10.1095/biolreprod.107.061804.CrossRefPubMed Xue Q, Lin Z, Cheng YH, Huang CC, Marsh E, Yin P, Milad MP, Confino E, Reierstad S, Innes J, Bulun SE: Promoter methylation regulates estrogen receptor 2 in human endometrium and endometriosis. Biol Reprod. 2007, 77: 681-687. 10.1095/biolreprod.107.061804.CrossRefPubMed
20.
go back to reference Borghese B, Mondon F, Noël JC, Fayt I, Mignot TM, Vaiman D, Chapron C: Gene expression profile for ectopic versus eutopic endometrium provides new insights into endometriosis oncogenic potential. Mol Endocrinol. 2008, 22: 2557-2562. 10.1210/me.2008-0322.CrossRefPubMed Borghese B, Mondon F, Noël JC, Fayt I, Mignot TM, Vaiman D, Chapron C: Gene expression profile for ectopic versus eutopic endometrium provides new insights into endometriosis oncogenic potential. Mol Endocrinol. 2008, 22: 2557-2562. 10.1210/me.2008-0322.CrossRefPubMed
21.
go back to reference Taylor HS, Bagot C, Kardana A, Olive D, Arici A: HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999, 14: 1328-1331. 10.1093/humrep/14.5.1328.CrossRefPubMed Taylor HS, Bagot C, Kardana A, Olive D, Arici A: HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999, 14: 1328-1331. 10.1093/humrep/14.5.1328.CrossRefPubMed
22.
go back to reference Lee B, Du H, Taylor HS: Experimental murine endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biol Reprod. 2009, 80: 79-85. 10.1095/biolreprod.108.070391.PubMedCentralCrossRefPubMed Lee B, Du H, Taylor HS: Experimental murine endometriosis induces DNA methylation and altered gene expression in eutopic endometrium. Biol Reprod. 2009, 80: 79-85. 10.1095/biolreprod.108.070391.PubMedCentralCrossRefPubMed
23.
go back to reference Cakmak H, Taylor HS: Molecular mechanisms of treatment resistance in endometriosis: the role of progesterone-hox gene interactions. Semin Reprod Med. 2010, 28: 69-74. 10.1055/s-0029-1242996.PubMedCentralCrossRefPubMed Cakmak H, Taylor HS: Molecular mechanisms of treatment resistance in endometriosis: the role of progesterone-hox gene interactions. Semin Reprod Med. 2010, 28: 69-74. 10.1055/s-0029-1242996.PubMedCentralCrossRefPubMed
24.
go back to reference Canis M, Donnez JG, Guzick DS, Halme JK, Rock JA, Schenken RS, et al: Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997, 67: 817-821. 10.1016/S0015-0282(97)81391-X.CrossRef Canis M, Donnez JG, Guzick DS, Halme JK, Rock JA, Schenken RS, et al: Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997, 67: 817-821. 10.1016/S0015-0282(97)81391-X.CrossRef
25.
go back to reference Tvarijonaviciene E, Nadisauskiene RJ: The value of hysterosalpingography in the diagnosis of tubal pathology among infertile patients. Medicina. 2008, 44: 439-448.PubMed Tvarijonaviciene E, Nadisauskiene RJ: The value of hysterosalpingography in the diagnosis of tubal pathology among infertile patients. Medicina. 2008, 44: 439-448.PubMed
26.
go back to reference Noyes RW, Hertig AT, Rock J: Dating the endometrial biopsy. Fertil Steril. 1950, 1: 3-5. Noyes RW, Hertig AT, Rock J: Dating the endometrial biopsy. Fertil Steril. 1950, 1: 3-5.
27.
go back to reference Ståhlberg A, Håkansson J, Xian X, Semb H, Kubista M: Properties of the reverse transcription reaction in mRNA quantification. Clin Chem. 2004, 50: 509-515. 10.1373/clinchem.2003.026161.CrossRefPubMed Ståhlberg A, Håkansson J, Xian X, Semb H, Kubista M: Properties of the reverse transcription reaction in mRNA quantification. Clin Chem. 2004, 50: 509-515. 10.1373/clinchem.2003.026161.CrossRefPubMed
28.
go back to reference Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988, 16: 1215-10.1093/nar/16.3.1215.PubMedCentralCrossRefPubMed Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988, 16: 1215-10.1093/nar/16.3.1215.PubMedCentralCrossRefPubMed
34.
go back to reference Krumlauf R: Mouse Hox genetic functions. Curr Opin Genet Dev. 1993, 3: 621-625. 10.1016/0959-437X(93)90098-A.CrossRefPubMed Krumlauf R: Mouse Hox genetic functions. Curr Opin Genet Dev. 1993, 3: 621-625. 10.1016/0959-437X(93)90098-A.CrossRefPubMed
35.
go back to reference Hsieh-Li HM, Witte DP, Weinstein M, Branford W, Li H, Small K, Potter SS: Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility. Development. 1995, 121: 1373-1385.PubMed Hsieh-Li HM, Witte DP, Weinstein M, Branford W, Li H, Small K, Potter SS: Hoxa 11 structure, extensive antisense transcription, and function in male and female fertility. Development. 1995, 121: 1373-1385.PubMed
36.
go back to reference Taylor HS, Vanden Heuvel GB, Igarashi P: A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod. 1997, 57: 1338-1345. 10.1095/biolreprod57.6.1338.CrossRefPubMed Taylor HS, Vanden Heuvel GB, Igarashi P: A conserved Hox axis in the mouse and human female reproductive system: late establishment and persistent adult expression of the Hoxa cluster genes. Biol Reprod. 1997, 57: 1338-1345. 10.1095/biolreprod57.6.1338.CrossRefPubMed
37.
go back to reference Benson GV, Lim H, Paria BC, Satokata I, Dey SK, Maas RL: Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression. Development. 1996, 122: 2687-2696.PubMed Benson GV, Lim H, Paria BC, Satokata I, Dey SK, Maas RL: Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression. Development. 1996, 122: 2687-2696.PubMed
38.
go back to reference Szczepańska M, Wirstlein P, Luczak M, Jagodziński PP, Skrzypczak J: Reduced expression of HOXA10 in the midluteal endometrium from infertile women with minimal endometriosis. Biomed Pharmacother. 2010, 64: 697-705. 10.1016/j.biopha.2010.09.012.CrossRefPubMed Szczepańska M, Wirstlein P, Luczak M, Jagodziński PP, Skrzypczak J: Reduced expression of HOXA10 in the midluteal endometrium from infertile women with minimal endometriosis. Biomed Pharmacother. 2010, 64: 697-705. 10.1016/j.biopha.2010.09.012.CrossRefPubMed
39.
go back to reference Taylor HS, Arici A, Olive D, Igarashi P: HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest. 1998, 101: 1379-1384.PubMedCentralCrossRefPubMed Taylor HS, Arici A, Olive D, Igarashi P: HOXA10 is expressed in response to sex steroids at the time of implantation in the human endometrium. J Clin Invest. 1998, 101: 1379-1384.PubMedCentralCrossRefPubMed
40.
go back to reference Taylor HS, Igarashi P, Olive DL, Arici A: Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metab. 1999, 84: 1129-1135. 10.1210/jc.84.3.1129.PubMed Taylor HS, Igarashi P, Olive DL, Arici A: Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium. J Clin Endocrinol Metab. 1999, 84: 1129-1135. 10.1210/jc.84.3.1129.PubMed
41.
go back to reference Rackow BW, Jorgensen E, Taylor HS: Endometrial polyps affect uterine receptivity. Fertil Steril. 2011, doi:10.1016/j.fertnstert.2010.12.034 Rackow BW, Jorgensen E, Taylor HS: Endometrial polyps affect uterine receptivity. Fertil Steril. 2011, doi:10.1016/j.fertnstert.2010.12.034
42.
go back to reference Ikegami K, Ohgane J, Tanaka S, Yagi S, Shiota K: Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development. Int J Dev Biol. 2009, 53: 203-214. 10.1387/ijdb.082741ki.CrossRefPubMed Ikegami K, Ohgane J, Tanaka S, Yagi S, Shiota K: Interplay between DNA methylation, histone modification and chromatin remodeling in stem cells and during development. Int J Dev Biol. 2009, 53: 203-214. 10.1387/ijdb.082741ki.CrossRefPubMed
43.
go back to reference Kim JJ, Taylor HS, Lu Z, Ladhani O, Hastings JM, Jackson KS, Wu Y, Guo SW, Fazleabas AT: Altered expression of HOXA10 in endometriosis: potential role in decidualization. Mol Hum Reprod. 2007, 13: 323-332. 10.1093/molehr/gam005.CrossRefPubMed Kim JJ, Taylor HS, Lu Z, Ladhani O, Hastings JM, Jackson KS, Wu Y, Guo SW, Fazleabas AT: Altered expression of HOXA10 in endometriosis: potential role in decidualization. Mol Hum Reprod. 2007, 13: 323-332. 10.1093/molehr/gam005.CrossRefPubMed
44.
go back to reference Fiegl H, Windbichler G, Mueller-Holzner E, Goebel G, Lechner M, Jacobs IJ, Widschwendter M: HOXA11 DNA methylation--a novel prognostic biomarker in ovarian cancer. Int J Cancer. 2008, 123: 725-729. 10.1002/ijc.23563.CrossRefPubMed Fiegl H, Windbichler G, Mueller-Holzner E, Goebel G, Lechner M, Jacobs IJ, Widschwendter M: HOXA11 DNA methylation--a novel prognostic biomarker in ovarian cancer. Int J Cancer. 2008, 123: 725-729. 10.1002/ijc.23563.CrossRefPubMed
45.
go back to reference Turek-Plewa J, Jagodziński PP: The role of mammalian DNA methyltransferases in the regulation of gene expression. Cell Mol Biol Lett. 2005, 10: 631-647.PubMed Turek-Plewa J, Jagodziński PP: The role of mammalian DNA methyltransferases in the regulation of gene expression. Cell Mol Biol Lett. 2005, 10: 631-647.PubMed
46.
go back to reference Wu Y, Strawn E, Basir Z, Halverson G, Guo SW: Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Fertil Steril. 2007, 87: 24-32. 10.1016/j.fertnstert.2006.05.077.CrossRefPubMed Wu Y, Strawn E, Basir Z, Halverson G, Guo SW: Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. Fertil Steril. 2007, 87: 24-32. 10.1016/j.fertnstert.2006.05.077.CrossRefPubMed
47.
go back to reference Lynch VJ, Brayer K, Gellersen B, Wagner GP: HoxA-11 and FOXO1A cooperate to regulate decidual prolactin expression: towards inferring the core transcriptional regulators of decidual genes. PLoS One. 2009, 4: e6845-10.1371/journal.pone.0006845.PubMedCentralCrossRefPubMed Lynch VJ, Brayer K, Gellersen B, Wagner GP: HoxA-11 and FOXO1A cooperate to regulate decidual prolactin expression: towards inferring the core transcriptional regulators of decidual genes. PLoS One. 2009, 4: e6845-10.1371/journal.pone.0006845.PubMedCentralCrossRefPubMed
48.
go back to reference Bao L, Tessier C, Prigent-Tessier A, Li F, Buzzio OL, Callegari EA, Horseman ND, Gibori G: Decidual prolactin silences the expression of genes detrimental to pregnancy. Endocrinology. 2007, 148: 2326-2334. 10.1210/en.2006-1643.CrossRefPubMed Bao L, Tessier C, Prigent-Tessier A, Li F, Buzzio OL, Callegari EA, Horseman ND, Gibori G: Decidual prolactin silences the expression of genes detrimental to pregnancy. Endocrinology. 2007, 148: 2326-2334. 10.1210/en.2006-1643.CrossRefPubMed
Metadata
Title
Expression of HOXA11 in the mid-luteal endometrium from women with endometriosis-associated infertility
Authors
Malgorzata Szczepańska
Przemyslaw Wirstlein
Jana Skrzypczak
Paweł P Jagodziński
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/10.1186/1477-7827-10-1

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