Fertility and Sterility
Volume 91, Issue 2 , Pages 489-499 , February 2009

Infertile women with isolated polycystic ovaries are deficient in endometrial expression of osteopontin but not αvβ3 integrin during the implantation window

  • Renée DuQuesnay, MRCOG

      Affiliations

    • Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom
  • ,
  • Corrina Wright, M.B., B.Ch.

      Affiliations

    • Department of Histopathology, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom
  • ,
  • Anita Abdul Aziz, Ph.D.

      Affiliations

    • Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom
  • ,
  • Gordon W.H. Stamp, FRCPath.

      Affiliations

    • Department of Histopathology, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom
  • ,
  • Geoffrey H. Trew, MRCOG

      Affiliations

    • Division of Paediatrics, Obstetrics and Gynaecology, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom
  • ,
  • Raul A. Margara, M.D.

      Affiliations

    • Division of Paediatrics, Obstetrics and Gynaecology, Imperial College London, Hammersmith Hospital, London W12 0NN, United Kingdom
  • ,
  • John O. White, Ph.D.

      Affiliations

    • Reproductive Biology Research Group, Institute of Life Science, Swansea University School of Medicine, Swansea, United Kingdom
    • Corresponding Author InformationReprint requests: John O. White, Ph.D., Reproductive Biology Research Group, Institute of Life Science, Swansea University School of Medicine, Swansea SA2 8PP, United Kingdom (FAX: 01792602280).

Received 30 July 2006 ,Revised 19 November 2007 ,Accepted 19 November 2007.

References 

  1. Yaron Y, Botchan A, Amit A, Kogosowski A, Yovel I, Lessing JB. Endometrial receptivity: the age-related decline in pregnancy rates and the effect of ovarian function. Fertil Steril. 1993;60:314–318
  2. Hertig AT, Rock J, Adams EC, Menkin MC. Thirty-four fertilized human ova, good, bad and indifferent, recovered from 210 women of known fertility; a study of biologic wastage in early human pregnancy. Pediatrics. 1959;23:202–211
  3. Navot D, Scott RT, Droesch K, Veeck LL, Liu HC, Rosenwaks Z. The window of embryo transfer and the efficiency of human conception in vitro. Fertil Steril. 1991;55:114–118
  4. Lessey BA. The use of integrins for the assessment of uterine receptivity. Fertil Steril. 1994;61:812–814
  5. Lessey BA, Damjanovich L, Coutifaris C, Castelbaum A, Albelda SM, Buck CA. Integrin adhesion molecules in the human endometrium. Correlation with the normal and abnormal menstrual cycle. J Clin Invest. 1992;90:188–195
  6. Tabibzadeh S. Patterns of expression of integrin molecules in human endometrium throughout the menstrual cycle. Hum Reprod. 1992;7:876–882
  7. Carson DD, Lagow E, Thathiah A, Al-Shami R, Farach-Carson MC, Vernon M, et al. Changes in gene expression during the early to mid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening. Mol Hum Reprod. 2002;8:871–879
  8. Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, et al. Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002;143:2119–2138
  9. Riesewijk A, Martin J, van Os R, Horcajadas JA, Polman J, Pellicer A, et al. Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology. Mol Hum Reprod. 2003;9:253–264
  10. Apparao KB, Murray MJ, Fritz MA, Meyer WR, Chambers AF, Truong PR, et al. Osteopontin and its receptor alphavbeta(3) integrin are coexpressed in the human endometrium during the menstrual cycle but regulated differentially. J Clin Endocrinol Metab. 2001;86:4991–5000
  11. Lessey BA, Castelbaum AJ. Integrins in the endometrium of women with endometriosis. Br J Obstet Gynaecol. 1995;102:347–348
  12. Gonzalez RR, Palomino A, Boric A, Vega M, Devoto L. A quantitative evaluation of alpha1, alpha4, alphaV and beta3 endometrial integrins of fertile and unexplained infertile women during the menstrual cycle. A flow cytometric appraisal. Hum Reprod. 1999;14:2485–2492
  13. Lessey BA, Castelbaum AJ, Sawin SW, Buck CA, Schinnar R, Bilker W, et al. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab. 1994;79:643–649
  14. Illera MJ, Lorenzo PL, Gui YT, Beyler SA, Apparao KB, Lessey BA. A role for alphavbeta3 integrin during implantation in the rabbit model. Biol Reprod. 2003;68:766–771
  15. Illera MJ, Cullinan E, Gui Y, Yuan L, Beyler SA, Lessey BA. Blockade of the alpha(v)beta(3) integrin adversely affects implantation in the mouse. Biol Reprod. 2000;62:1285–1290
  16. Johnson GA, Burghardt RC, Bazer FW, Spencer TE. Osteopontin: roles in implantation and placentation. Biol Reprod. 2003;69:1458–1471
  17. Christensen B, Nielsen MS, Haselmann KF, Petersen TE, Sorensen ES. Post-translationally modified residues of native human osteopontin are located in clusters: identification of 36 phosphorylation and five O-glycosylation sites and their biological implications. Biochem J. 2005;390:285–292
  18. Aplin JD. Adhesion molecules in implantation. Rev Reprod. 1997;2:84–93
  19. von Wolff M, Strowitzki T, Becker V, Zepf C, Tabibzadeh S, Thaler CJ. Endometrial osteopontin, a ligand of beta3-integrin, is maximally expressed around the time of the “implantation window.”. Fertil Steril. 2001;76:775–781
  20. Franzen A, Heinegard D. Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem J. 1985;232:715–724
  21. Senger DR, Perruzzi CA, Papadopoulos A, Tenen DG. Purification of a human milk protein closely similar to tumor-secreted phosphoproteins and osteopontin. Biochim Biophys Acta. 1989;996:43–48
  22. Luedtke CC, McKee MD, Cyr DG, Gregory M, Kaartinen MT, Mui J, et al. Osteopontin expression and regulation in the testis, efferent ducts, and epididymis of rats during postnatal development through to adulthood. Biol Reprod. 2002;66:1437–1448
  23. Brown LF, Berse B, Van de Water L, Papadopoulos-Sergiou A, Perruzzi CA, Manseau EJ, et al. Expression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces. Mol Biol Cell. 1992;3:1169–1180
  24. Hotte SJ, Winquist EW, Stitt L, Wilson SM, Chambers AF. Plasma osteopontin: associations with survival and metastasis to bone in men with hormone-refractory prostate carcinoma. Cancer. 2002;95:506–512
  25. Miyauchi A, Alvarez J, Greenfield EM, Teti A, Grano M, Colucci S, et al. Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts. J Biol Chem. 1991;266:20369–20374
  26. Flores ME, Norgard M, Heinegard D, Reinholt FP, Andersson G. RGD-directed attachment of isolated rat osteoclasts to osteopontin, bone sialoprotein, and fibronectin. Exp Cell Res. 1992;201:526–530
  27. Hruska KA, Rolnick F, Huskey M, Alvarez U, Cheresh D. Engagement of the osteoclast integrin alpha v beta 3 by osteopontin stimulates phosphatidylinositol 3-hydroxyl kinase activity. Ann N Y Acad Sci. 1995;760:151–165
  28. Senger DR, Perruzzi CA. Cell migration promoted by a potent GRGDS-containing thrombin-cleavage fragment of osteopontin. Biochim Biophys Acta. 1996;1314:13–24
  29. Agnihotri R, Crawford HC, Haro H, Matrisian LM, Havrda MC, Liaw L. Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin). J Biol Chem. 2001;276:28261–28267
  30. Kousta E, White DM, Cela E, McCarthy MI, Franks S. The prevalence of polycystic ovaries in women with infertility. Hum Reprod. 1999;14:2720–2723
  31. Adams JM, Taylor AE, Crowley WF, Hall JE. Polycystic ovarian morphology with regular ovulatory cycles: insights into the pathophysiology of polycystic ovarian syndrome. J Clin Endocrinol Metab. 2004;89:4343–4350
  32. Apparao KB, Lovely LP, Gui Y, Lininger RA, Lessey BA. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome. Biol Reprod. 2002;66:297–304
  33. Cermik D, Selam B, Taylor HS. Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88:238–243
  34. Palomino WA, Fuentes A, Gonzalez RR, Gabler F, Boric MA, Vega M, et al. Differential expression of endometrial integrins and progesterone receptor during the window of implantation in normo-ovulatory women treated with clomiphene citrate. Fertil Steril. 2005;83:587–593
  35. Brosens J, Verhoeven H, Campo R, Gianaroli L, Gordts S, Hazekamp J, et al. High endometrial aromatase P450 mRNA expression is associated with poor IVF outcome. Hum Reprod. 2004;19:352–356
  36. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81:19–25
  37. Adams J, Polson DW, Franks S. Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. Br Med J (Clin Res Ed). 1986;293:355–359
  38. Noyes RW, Haman JO. Accuracy of endometrial dating; correlation of endometrial dating with basal body temperature and menses. Fertil Steril. 1953;4:504–517
  39. Chambers AF, Wilson SM, Kerkvliet N, O'Malley FP, Harris JF, Casson AG. Osteopontin expression in lung cancer. Lung Cancer. 1996;15:311–323
  40. Bautista DS, Xuan JW, Hota C, Chambers AF, Harris JF. Inhibition of Arg-Gly-Asp (RGD)-mediated cell adhesion to osteopontin by a monoclonal antibody against osteopontin. J Biol Chem. 1994;269:23280–23285
  41. Budwit-Novotny DA, McCarty KS, Cox EB, Soper JT, Mutch DG, Creasman WT, et al. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res. 1986;46:5419–5425
  42. Fisher LW, Stubbs JT, Young MF. Antisera and cDNA probes to human and certain animal model bone matrix noncollagenous proteins. Acta Orthop Scand Suppl. 1995;266:61–65
  43. Ruck P, Marzusch K, Kaiserling E, Horny HP, Dietl J, Geiselhart A, et al. Distribution of cell adhesion molecules in decidua of early human pregnancy. An immunohistochemical study. Lab Invest. 1994;71:94–101
  44. Aplin JD, Spanswick C, Behzad F, Kimber SJ, Vicovac L. Integrins beta 5, beta 3 and alpha v are apically distributed in endometrial epithelium. Mol Hum Reprod. 1996;2:527–534
  45. Borthwick JM, Charnock-Jones DS, Tom BD, Hull ML, Teirney R, Phillips SC, et al. Determination of the transcript profile of human endometrium. Mol Hum Reprod. 2003;9:19–33
  46. Craig AM, Denhardt DT. The murine gene encoding secreted phosphoprotein 1 (osteopontin): promoter structure, activity, and induction in vivo by estrogen and progesterone. Gene. 1991;100:163–171
  47. Omigbodun A, Ziolkiewicz P, Tessler C, Hoyer JR, Coutifaris C. Progesterone regulates osteopontin expression in human trophoblasts: a model of paracrine control in the placenta?. Endocrinology. 1997;138:4308–4315
  48. Homburg R. Polycystic ovary syndrome—from gynaecological curiosity to multisystem endocrinopathy. Hum Reprod. 1996;11:29–39
  49. Hassan MA, Killick SR. Ultrasound diagnosis of polycystic ovaries in women who have no symptoms of polycystic ovary syndrome is not associated with subfecundity or subfertility. Fertil Steril. 2003;80:966–975
  50. Esinler I, Bayar U, Bozdag G, Yarali H. Outcome of intracytoplasmic sperm injection in patients with polycystic ovary syndrome or isolated polycystic ovaries. Fertil Steril. 2005;84:932–937
  51. Xuan JW, Hota C, Chambers AF. Recombinant GST-human osteopontin fusion protein is functional in RGD-dependent cell adhesion. J Cell Biochem. 1994;54:247–255
  52. Holinka CF, Hata H, Kuramoto H, Gurpide E. Responses to estradiol in a human endometrial adenocarcinoma cell line (Ishikawa). J Steroid Biochem. 1986;24:85–89
  53. Osyczka AM, Leboy PS. Bone morphogenetic protein regulation of early osteoblast genes in human marrow stromal cells is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling. Endocrinology. 2005;146:3428–3437
  54. Knippenberg M, Helder MN, Zandieh Doulabi B, Wuisman PI, Klein-Nulend J. Osteogenesis versus chondrogenesis by BMP-2 and BMP-7 in adipose stem cells. Biochem Biophys Res Commun. 2006;342:902–908
  55. Kusumegi T, Tanaka J, Kawano M, Yonemoto J, Tohyama C, Sone H. BMP7/ActRIIB regulates estrogen-dependent apoptosis: new biomarkers for environmental estrogens. J Biochem Mol Toxicol. 2004;18:1–11

 R.D. has nothing to disclose. C.W. has nothing to disclose. A.A.A. has nothing to disclose. G.W.H.S. has nothing to disclose. G.H.T. has nothing to disclose. R.A.M. has nothing to disclose. J.O.W. has nothing to disclose.

 Supported by The Wellcome Trust, Grant Number 069773/Z/02/Z, and The Institute of Obstetrics and Gynaecology Trust Fund, Hammersmith Hospital.

PII: S0015-0282(07)04129-5

doi: 10.1016/j.fertnstert.2007.11.063

Fertility and Sterility
Volume 91, Issue 2 , Pages 489-499 , February 2009