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Hyaluronic Acid Inhibits Apoptosis in Granulosa Cells via CD44

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Abstract

Purpose: This study was designed to examine whether hyaluronicacid (HA) inhibits apoptosis in cumulus and muralgranulosa cells and to examine whether this effect of HAwas mediated through CD44.

Methods: Mural and cumulus granulosa cells were obtainedfrom in vitro fertilization patients. The cells were culturedwith various concentrations of HA or HA plus variousconcentrations of anti-CD44 antibody without serum supplement.After 24 hr of culture, the cells were fixed and stainedwith Hoechst 33258. One thousand granulosa cells of eachconditions were observed by fluorescence microscopy.

Results: HA inhibited apoptosis in both kinds of granulosacells, and anti-CD44 antibody prevented this effect of HA.Conclusions: The incidence of apoptotic granulosa cellswith fragmented condensed nuclei was reduced by HA viaCD44.

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REFERENCES

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

    Google Scholar 

  2. Turley EA: Hyaluronan and cell locomotion. Cancer Metastasis Rev 1992;11:21–30

    Google Scholar 

  3. Sato E, Ishibashi T, Koide SS: Prevention of spontaneous degeneration of mouse oocytes in culture by ovarian glycosaminoglycans. Biol Reprod 1987;37:371–376

    Google Scholar 

  4. Miyano T, Hiro-oka E, Kano K, Miyake M, Kusunoki H, Kato S: Effect of hyaluronic acid on the development of 1–and 2–cell porcine embryos to the blastocyst stage in vitro. Theriogeniology 1994;41:1299–1305

    Google Scholar 

  5. Tilly JL, Kowalski KI, Johnson AL, Hsueh AJW: Involvement of apoptosis in ovarian follicle atresia and postovulatory regression. Endocrinology 1991;129:2799–2801

    Google Scholar 

  6. Piquette GN, Tilly JL, Prichard LE, Simon C, Polan ML: Detection of apoptosis in human and rat ovarian follicles. J Soc Gynecol Invest 1994;1(4):297–301

    Google Scholar 

  7. Leoncini L, Del Vecchio MT, Megha T, Barbini P, Galieni P, Pileri S, Sabattini E, Gherlinozi F, Tosi P, Kraft R, Cottier H: Correlation between apoptotic and proliferative indices in malignant non-Hodgkin's lymphoma. Am J Pathol 1993;142: 755–763

    Google Scholar 

  8. Wheeler TM, Roger E, Aihara M, Scardino PT, Thompson TC: Apoptotic index as a biomarker in prostatic intraepithelial neoplasma (PIN) and prostatic cancer. J Cell Biol 1994;19: 202–207

    Google Scholar 

  9. Nakahara K, Saito H, Saito T, Ito MM, Ohta N, Sakai N, Tezuka N, Hiroi M, Watanabe H: Incidence of apoptotic bodies in membrana granulosa of the patients participating in an in vitro fertilization programs. Fertil Steril 1997;67:302–308

    Google Scholar 

  10. Culty M, Miyake K, Kincade PW, Sikorski E, Butcher EC, Underhill C, Silorki E: The hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins. J Cell Biol 1990;111:2765–2774

    Google Scholar 

  11. Underhill C: CD44; The hyaluronan receptor. J Cell Sci 1992;103:293–298

    Google Scholar 

  12. Knudson CB, Knudson W: Hyaluronan-binding proteins in development, tissue homeostasis and disease. FASEB J 1993;7: 1233–1241

    Google Scholar 

  13. Campbell S, Swann HR, Aplin JD, Seif MW, Kimber SJ, Elstein M: CD44 expressed throughout pre-implantation human embryo development. Hum Reprod 1995;10:425–430

    Google Scholar 

  14. Ohta N, Saito H, Kuzumaki T, Takahashi T, Ito MM, Saito T, Nakahara K, Hiroi M: Expression of CD44 in human cumulus and mural granulosa cells of individual patients in in vitro fertilization programmes. Mol Hum Reprod 1999;5:22–28

    Google Scholar 

  15. Nakahara K, Saito H, Saito T, Ito MM, Ohta N, Takahashi T, Hiroi M: Ovarian fecundity in patients with endometriosis can be estimated by the incidence of apoptotic bodies. Fertil Steril 1998;69:931–935

    Google Scholar 

  16. Guthrie HD, Welch GH, Cooper BS, Zakaria AD, Johnson LA: Flow cytometric determination of degraded deoxyribonucleic acid in granulosa cells to identify atretic follicles during preovulatory maturation in the pig. Biol Reprod 1994;50:1303–1311

    Google Scholar 

  17. Samuel SK, Hurta RA, Spearman MA, Wright JA, Turley EA, Greenberg AH: TGF-beta 1 stimulation of cell locomotion utilizes the hyaluronan receptor RHAMM and hyaluronan. J Cell Biol 1993;123:349–358

    Google Scholar 

  18. Zhang L, Underhill CB, Chen L: Hyaluronan on the surface of tumor cells is correlated with metastatic behavior. Cancer Res 1995;55:428–433

    Google Scholar 

  19. West DC, Kumar S: Hyaluronan and angiogenesis. In The Biology of Hyaluronan, Chichester, England, Wiley-Interscience, 1989, pp 189–207

    Google Scholar 

  20. Lees VC, Fan TP, West DC: Angiogenesis in a delayed revascularization model is accelerated by angiogenic oligosaccharides of hyaluronan. Lab Invest 1995;73(2):259–66

    Google Scholar 

  21. Dick SJ, Macchi B, Papazoglou S, Oldfield EH, Kornblith PL, Smith BH, Gately MK: Lymphoid cell-glioma cell interaction enhances cell coat production by human gliomas: Novel suppresser mechanism. Science 1983;220:739–742

    Google Scholar 

  22. Chen L, Russell PT, Larsen WJ: Functional significance of cumulus expansion in the mouse: Roles for the preovulatory synthesis of hyaluronic acid within the cumulus mass. Mol Reprod Dev 1993;34:87–93

    Google Scholar 

  23. Ayroldi E, Cannarile L, Migliorati G, Bartoli A, Nicoletti I, Riccardi C: CD44 (Pgp-1) inhibits CD3 and dexamethason-induced apoptosis. Blood 1995;86:2672–2678

    Google Scholar 

  24. Peluso JJ, Pappalardo A, Trolice MP: N-cadherin-mediated cell contact inhibits granulosa cell apoptosis in a progesterone-independent manner. Endocrinology 1996;137:1196–1203

    Google Scholar 

  25. Saito H, Saito T, Hirayama T, Nohara M, Koike K, Hiroi M: Cumulus mass maintains embryo quality. Fertil Steril 1994;62: 555–558

    Google Scholar 

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Kaneko, T., Saito, H., Toya, M. et al. Hyaluronic Acid Inhibits Apoptosis in Granulosa Cells via CD44. J Assist Reprod Genet 17, 162–167 (2000). https://doi.org/10.1023/A:1009470206468

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  • DOI: https://doi.org/10.1023/A:1009470206468

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