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Disrupted hyaluronan binding protein 1 (HABP1) expression: one of the key mediator for ovarian dysfunction in polycystic ovary rat

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Abstract

Proper follicular development is crucial for cumulus-oocyte complex (COC) maturation, ovulation and luteinisation. All these ovarian processes are regulated by finely tuned rapid tissue remodeling that involves hyaluronan and interconnecting hyaladherins-rich extracellular matrix synthesis and its breakdown by various proteinase systems like matrix metalloproteinase (MMP). Disrupted tissue remodeling machinery can result into pathophysiologies like atretic follicular cysts formation in polycystic ovary syndrome (PCOS). In present study, we employ superovulated (SO) and polycystic ovary (PCO) rat models and demonstrate that on contrary to SO, PCO rat ovary illustrates abnormal follicular morphology with differential levels of various ovarian factors [like HA (hyaluronan), TSG-6 (TNF-α-stimulated gene/protein 6), PTX-3 (pentraxin-3), HABP1 (hyaluronan binding protein 1), MMP2 (matrix metalloproteinase), MT1-MMP (membrane type 1-matrix metalloproteinase) and COX2 (Cyclooxygenase-2)] along with hyperactivities of gelatinases (like MMP9 and -2). Besides cultured COC expansion is blocked by anti-HABP1 antibody treatment showing reduced HABP1 expression. Overall, as MT1-MMP has inverse relation with HABP1 level and direct effect on MMP2 activity, the observations from current in vivo and in vitro studies indicate that disrupted ovarian HABP1 along with concurrent altered expression and hyperactivation of related MMPs can lead to abnormal follicular maturation resulting into ovarian dysfunction in PCO rat.

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References

  1. Ehrmann DA, Barnes RB, Rosenfield RL (1995) Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Endocrin Rev 16:322–353

    Article  CAS  Google Scholar 

  2. Legro RS (1998) Polycystic ovary syndrome: current and future treatment paradigms. Am J Obstet Gynecol 179:S101–S108

    Article  CAS  PubMed  Google Scholar 

  3. Shalev E, Goldman S, Ben-Shlomo I (2001) The balance between MMP9 and MMP2 and their tissue inhibitor (TIMP)-1 in luteinized granulosa cells: comparison between women with PCOS and normal ovulatory women. Mol Hum Reprod 7:325–331

    Article  CAS  PubMed  Google Scholar 

  4. Goldman S, Shalev E (2004) MMPS and TIMPS in ovarian physiology and pathophysiology. Front Biosci 9:2474–2483

    Article  CAS  PubMed  Google Scholar 

  5. Honnma H, Endo T, Henmi H, Nagasawa K, Baba T, Yamazaki K, Kitajima Y, Hayashi T, Manase K, Saito T (2006) Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats. Apoptosis 11:1525–1533

    Article  CAS  PubMed  Google Scholar 

  6. Ochsner SA, Day AJ, Rugg MS (2003) Disrupted function of tumor necrosis factor-alfa-stimulated gene 6 blocks cumulus cell-oocyte complex expansion. Endocrinology 144:4376–4384

    Article  CAS  PubMed  Google Scholar 

  7. Scarchilli L, Camaioni A, Bottazzi B, Negri V, Doni A, Deban L, Bastone A, Salvatori G, Mantovani A, Siracusa G, Salustri A (2007) PTX3 interacts with inter-alpha-trypsin inhibitor: implications for hyaluronan organization and cumulus oophorus expansion. J Biol Chem 282:30161–30170

    Article  CAS  PubMed  Google Scholar 

  8. Tosi F, Di Sarra D, Bonin C, Zambotti F, Dall’alda M, Fiers T, Kaufman JM, Donati M, Franchi M, Zanolin ME, Bonora E, Moghetti P (2014) Plasma levels of pentraxin-3, an inflammatory protein involved in fertility, are reduced in women with polycystic ovary syndrome. Eur J Endocrinol 170:401–409

    Article  CAS  PubMed  Google Scholar 

  9. Thakur SC, Datta K (2008) Higher expression of hyaluronan binding protein 1 (HABP1/p32/gC1qR/SF2) during follicular development and cumulus oocyte complex maturation in rat. Mol Reprod Dev 75:429–438

    Article  CAS  PubMed  Google Scholar 

  10. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  CAS  PubMed  Google Scholar 

  11. Tempel C, Gilead A, Neeman M (2000) Hyaluronic acid as an anti-angiogenic shield in the preovulatory rat follicle. Biol Reprod 63:134–140

    Article  CAS  PubMed  Google Scholar 

  12. Tsafriri A (1995) Ovulation as a tissue remodeling process. Proteolysis and cumulus expansion. Adv Exp Med Biol 377:121–140

    Article  CAS  PubMed  Google Scholar 

  13. Liu K, Olofsson JI, Wahlberg P, Ny T (1999) Distinct expression of gelatinase A [Matrix metalloproteinase (MMP)-2], collagenase-3 (MMP13), membrane type MMP 1 (MMP14), and tissue inhibitor of MMPs type 1 mediated by physiological signals during formation and regression of the rat corpus luteum. Endocrinology 140:5330–5338

    CAS  PubMed  Google Scholar 

  14. Smith MF, McIntush EW, Ricke WA, Kojima FN, Smith GW (1999) Regulation of ovarian extracellular matrix remodeling by metalloproteinases and their tissue inhibitors: effects on follicular development, ovulation and luteal function. J Reprod Fertil Suppl 54:367–381

    CAS  PubMed  Google Scholar 

  15. Smith MF, Ricke WA, Bakke LJ, Dow MPD, Smith GW (2002) Ovarian tissue remodeling: role of matrix metalloproteinases and their inhibitors. Mol Cell Endocrinol 191:45–56

    Article  CAS  PubMed  Google Scholar 

  16. Sanchez-Criado JE, Sanchez A, Ruiz A, Gaytan F (1993) Endocrine and morphological features of cystic ovarian condition in antiprogesterone RU486-treated rats. Acta Endocrinol (Copenhagen) 129:237–245

    CAS  Google Scholar 

  17. Gaytán F, Bellido C, Gaytán M, Morales C, Sánchez-Criado JE (2003) Differential effects of RU486 and indomethacin on follicle rupture during the ovulatory process in the rat. Biol Reprod 69:99–105

    Article  PubMed  Google Scholar 

  18. Gaytan M, Bellido C, Morales C, Gonzalez-Padilla M, Sanchez-Criado JE, Gaytan F (2004) Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions. Reprod Biol Endocrinol 2:63

    Article  PubMed Central  PubMed  Google Scholar 

  19. Salustri A, Yanagishita M, Underhill CB, Laurent TC, Hascall VC (1992) Localization and synthesis of hyaluronic acid in the cumulus cells and mural granulosa cells of the preovulatory follicle. Dev Biol 151:541–551

    Article  CAS  PubMed  Google Scholar 

  20. Yoshioka S, Ochsner S, Russell DL (2000) Expression of tumor necrosis factor-stimulated gene-6 in the rat ovary in response to an ovulatory dose of gonadotropin. Endocrinology 141:4114–4119

    CAS  PubMed  Google Scholar 

  21. Salustri A, Garlanda C, Hirsch E (2004) PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization. Development 131:1577–1586

    Article  CAS  PubMed  Google Scholar 

  22. Fulop C, Kamath RV, Li Y (1997) Coding sequence, exon–intron structure and chromosomal localization of murine TNF-stimulated gene 6 that is specifically expressed by expanding cumulus cell-oocyte complexes. Gene 202:95–102

    Article  CAS  PubMed  Google Scholar 

  23. Toshifumi T, Jason DM, Haibin W, Sudhansu K Dey (2006) Cyclooxygenase-2-derived prostaglandin E2 directs oocyte maturation by differentially influencing multiple signaling pathways. J Biol Chem 281:37117–37129

    Article  Google Scholar 

  24. Rozanov DV, Ghebrehiwet B, Ratnikova BI, Monosova EZ, Deryuginaa EI, Strongina AY (2002) The cytoplasmic tail peptide sequence of membrane type-1 matrix metalloproteinase (MT1-MMP) directly binds to gC1qR, a compartment-specific chaperone-like regulatory protein. FEBS Lett 527:51–57

    Article  CAS  PubMed  Google Scholar 

  25. Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, Seiki M (1994) A matrix metalloproteinase expressed on the surface of invasive tumor cells. Nature 370:61–65

    Article  CAS  PubMed  Google Scholar 

  26. Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA, Goldberg GI (1995) Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease. J Biol Chem 270:5331–5338

    Article  CAS  PubMed  Google Scholar 

  27. Brooks PC, Strömblad S, Sanders LC, von Schalscha TL, Aimes R, Stetle Stevenson WG, Quigley JP, Cheresh DA (1996) Localization of matrix metalloproteinase MMP2 to the surface of cells by interaction with integrin αvβ3. Cell 85:683–693

    Article  CAS  PubMed  Google Scholar 

  28. Butler GS, Butler MJ, Atkinson SJ, Will H, Tamura T, Schade van Westrum S, Crabbe T, Clements J, d’Ortho MP, Murphy G (1998) The TIMP2 membrane type 1 metalloproteinase ‘receptor’ regulates the concentration and efficient activation of progelatinase A: a kinetic study. J Biol Chem 273:871–880

    Article  CAS  PubMed  Google Scholar 

  29. Deryugina EI, Ratnkov B, Monosov E, Postnova TI, Discipio R, Smith JW, Strongin AY (2001) MT1-MMP initiates activation of pro-MMP2 and integrin αvβ3 promotes maturation of MMP2 in breast carcinoma cells. Exp Cell Res 263:209–223

    Article  CAS  PubMed  Google Scholar 

  30. Sakaki H, Matsumiya T, Kusumi A, Imaizumi T, Satoh H, Yoshida H, Satoh K, Kimura H (2004) Interleukin-1 beta induces matrix metalloproteinase-1 expression in cultured human gingival fibroblasts: role of cyclooxygenase-2 and prostaglandin E2. Oral Dis 10:87–93

    Article  CAS  PubMed  Google Scholar 

  31. Falcone DJ, Sakamoto K, Steenport ML, Khan KMF, Du B, Dannenberg AJ (2007) Interleukin 6 stimulates macrophage MMP9 expression via COX-2-dependent induction of PGE2 synthesis and engagement of the EP4 receptor. FASEB J 21(383):3

    Google Scholar 

  32. Birkedal-Hansen H (1993) Role of cytokines and inflammatory mediators in tissue destruction. J Periodontal Res 28:500–510

    Article  CAS  PubMed  Google Scholar 

  33. Garcı´a-Redondo AB, Briones AM, Beltra´n AE, Alonso MJ, Simonsen U, Salaices M (2009) Hypertension increases contractile responses to hydrogen peroxide in resistance arteries through increased thromboxane A2, Ca2+, and superoxide anion levels. J Pharmacol Exp Ther 328:19–27

    Article  Google Scholar 

  34. Tang EH, Leung FP, Huang Y, Feletou M, So KF, Man RY, Vanhoutte PM (2007) Calcium and reactive oxygen species increase in endothelial cells in response to releasers of endothelium derived contracting factor. Br J Pharmacol 151:15–23

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Sancho P, Martı´n-Sanz P, Fabregat I (2011) Reciprocal regulation of NADPH oxidases and the cyclooxygenase-2 pathway. Free Radic Biol Med 51:1789–1798

    Article  CAS  PubMed  Google Scholar 

  36. Devine Patrick J, Perreault Sally D, Ulrike Luderer (2012) Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biol Reprod 86:27

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Murri M, Luque-Ramírez M, Insenser M, Ojeda-Ojeda M, Escobar-Morreale HF (2013) Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Hum Reprod Update 19:268–288

    Article  CAS  PubMed  Google Scholar 

  38. Chang H (2002) Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev 23:787–823

    Article  CAS  PubMed  Google Scholar 

  39. Vanderhyden BC, Macdonald EA, Nagyova E, Dhawan A (2003) Evaluation of members of the TGF-beta superfamily as candidates for the oocyte factors that control mouse cumulus expansion and steroidogenesis. Reprod Suppl 61:55–70

    CAS  PubMed  Google Scholar 

  40. Russell DL, Salustri A (2006) Extracellular matrix of the cumulus-oocyte complex. Semin Reprod Med 24:217–227

    Article  CAS  PubMed  Google Scholar 

  41. Eppig JJ (1981) Prostaglandin E2 stimulates cumulus expansion and hyaluronic acid synthesis by cumuli oophori isolated from mice. Biol Reprod 25:191–195

    Article  CAS  PubMed  Google Scholar 

  42. Downs SM, Longo FJ (1983) Prostaglandins and preovulatory follicular maturation in mice. J Exp Zool 228:99–108

    Article  CAS  PubMed  Google Scholar 

  43. Davis BJ, Lennard DE, Lee CA, Tiano HF, Morham SG, Wetsel WC, Langenbach R (1999) Anovulation in cyclooxygenase-2-deficient mice is restored by prostaglandin E2 and interleukin-1β. Endocrinology 140:2685–2695

    CAS  PubMed  Google Scholar 

  44. Ochsner SA, Russell DL, Day AJ (2003) Decreased expression of tumor necrosis factor-alpha-stimulated gene 6 in cumulus cells of the cyclooxygenase-2 and EP2 null mice. Endocrinology 144:1008–1019

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We gratefully acknowledge the financial support received from Indian Council of Medical Research, New Delhi, India; to perform the present study. We are indebted to Dr. Ilora Ghosh, Assistant Professor, School of Environmental Sciences, Jawaharlal Nehru University, Delhi, India for allowing us to utilize all the laboratory facilities.

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Authors and Affiliations

  1. Biochemistry and Toxicology Laboratory, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi, 110067, India

    Mohammed Arif & Kasturi Datta

  2. Reproductive Toxicology Laboratory, Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia University, New Delhi, 110025, India

    Mohammed Arif & Sonu Chand Thakur

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  1. Mohammed Arif
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  2. Sonu Chand Thakur
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Correspondence to Sonu Chand Thakur or Kasturi Datta.

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Arif, M., Thakur, S.C. & Datta, K. Disrupted hyaluronan binding protein 1 (HABP1) expression: one of the key mediator for ovarian dysfunction in polycystic ovary rat. Mol Cell Biochem 398, 233–244 (2015). https://doi.org/10.1007/s11010-014-2224-y

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