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Lysophosphatidic acid stimulates hyaluronan production by mouse cumulus–oocyte complexes

  • Original Article
  • Published:
Reproductive Medicine and Biology

Abstract

Purpose

In mammals, cumulus expansion due to increased synthesis of hyaluronan was suggested to correlate with modification of the gap junction between cumulus cells and the oocyte, leading to cumulus expansion. We examined whether lysophosphatidic acid, a lipid mediator detected in mammalian body fluids, stimulates significant production of hyaluronan and thus affects mouse cumulus expansion in vitro.

Methods

Cumulus–oocyte complexes isolated from the gonadotropin-treated ovaries of B6C3F1 mice were exposed to lysophosphatidic acid in the presence and absence of 0.3 % fetal bovine serum for measurement of cumulus expansion and released hyaluronan, respectively.

Results

Exogenously added lysophosphatidic acid concentration-dependently stimulated production of hyaluronan in the cumulus cell–oocyte complex, and the stimulatory effect of lysophosphatidic acid on hyaluronan production was mediated through the signal pathways, including LPA receptor-Gi coupling, EGF receptor transactivation, and activations of phosphatidylinositol-specific phospholipase C, protein kinase C and mitogen-activated protein kinases. LPA increased mRNA expression of tumor necrosis α-induced protein 6, a hyaluronan-binding protein, and expansion of cumulus cell–oocyte complex.

Conclusions

Lysophosphatidic acid in follicular fluids may participate in physiological cumulus expansion before ovulation by stimulating production of hyaluronan and proteins that enable the association of hyaluronan with cumulus cells and oocytes.

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References

  1. Edry I, Sela-Abramovich S, Dekel N. Meiotic arrest of oocytes depends on cell-to-cell communication in the ovarian follicle. Mol Cell Endocrinol. 2006;252:102–6.

    Article  CAS  PubMed  Google Scholar 

  2. Eppig JJ. FSH stimulates hyaluronic acid synthesis by oocyte-cumulus cell complexes from mouse preovulatory follicles. Nature. 1979;281:483–4.

    Article  CAS  PubMed  Google Scholar 

  3. Hess KA, Chen L, Larsen WJ. Inter-α-inhibitor binding to hyaluronan in the cumulus extracellular matrix is required for optimal ovulation and development of mouse oocytes. Biol Reprod. 1999;61:436–43.

    Article  CAS  PubMed  Google Scholar 

  4. Allworth AE, Albertini DF. Meiotic maturation in cultured bovine oocytes is accompanied by remodeling of the cumulus cell cytoskeleton. Dev Biol. 1993;158:101–12.

    Article  CAS  PubMed  Google Scholar 

  5. Larsen WJ, Wert SE, Brunner GD. A dramatic loss of cumulus cell gap junctions is correlated with germinal vesicle breakdown in rat oocytes. Dev Biol. 1986;3:517–21.

    Article  Google Scholar 

  6. Eppig JJ. Role of serum in FSH stimulated cumulus expansion by mouse oocyte-cumulus cell complexes in vitro. Biol Reprod. 1980;22:629–33.

    CAS  PubMed  Google Scholar 

  7. Kimura N, Konno Y, Miyoshi K, Matsumoto H, Sato E. Expression of hyaluronan synthases and CD44 messenger RNAs in porcine cumulus-oocyte complexes during in vitro maturation. Biol Reprod. 2002;66:707–17.

    Article  CAS  PubMed  Google Scholar 

  8. Schoenfelder M, Einspanier R. Expression of hyaluronan synthase and corresponding hyaluronan receptors is differentially regulated during oocyte maturation in cattle. Biol Reprod. 2003;69:269–77.

    Article  CAS  PubMed  Google Scholar 

  9. Nagyova E, Camaioni A, Prochazka R, Salustri A. Covalent transfer of heavy chains of inter-α-trypsin inhibitor family proteins to hyaluronan in in vivo and in vitro expanded porcine oocyte-cumulus complexes. Biol Reprod. 2004;71:1838–43.

    Article  CAS  PubMed  Google Scholar 

  10. Tokumura A. A family of phospholipid autacoid: occurrence, metabolism and bioactions. Prog Lipid Res. 1995;4:151–84.

    Article  Google Scholar 

  11. Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, Lin ME, Teo ST, Park KE, Mosley AN, Chun J. LPA receptors: subtypes and biological actions. Annu Rev Pharmacol Toxicol. 2010;50:157–86.

    Article  CAS  PubMed  Google Scholar 

  12. Hinokio K, Yamano S, Nakagawa K, Irahara M, Kamada, Tokumura A, Aono T. Lysophosphatidic acid stimulates nuclear and cytoplasmic maturation of golden hamster immature oocytes in vitro via cumulus cells. Life Sci. 2002;70:759–67.

    Article  CAS  PubMed  Google Scholar 

  13. Komatsu J, Yamano S, Kuwahara A, Tokumura A, Irahara M. The signaling pathways linking to lysophosphatidic acid-promoted meiotic maturation in mice. Life Sci. 2006;79:506–11.

    Article  CAS  PubMed  Google Scholar 

  14. Kunikata K, Yamano S, Tokumura A, Aono T. Effect of lysophosphatidic acid on the ovum transport in mouse oviducts. Life Sci. 1999;65:833–40.

    Article  CAS  PubMed  Google Scholar 

  15. Kobayashi T, Yamano S, Murayama S, Ishikawa H, Tokumura A, Aono T. Effect of the preimplantation development of mouse embryos. FEBS Lett. 1994;351:38–40.

    Article  CAS  PubMed  Google Scholar 

  16. Tokumura A. Metabolic pathways and physiological and pathophysiological significances of lysolipid phosphate mediators. J Cell Biochem. 2004;9(92):869–81.

    Article  CAS  Google Scholar 

  17. Tokumura A, Miyake M, Nishioka Y, Yamano S, Aono T, Fukuzawa K. Production of lysophosphatidic acids by lysophospholipase D in human follicular fluids of in vitro fertilization patients. Biol Reprod. 1999;61:195–9.

    Article  CAS  PubMed  Google Scholar 

  18. Fülöp C, Szánto S, Mukhopadhay D, Bárdos T, Kmath RV, Rugg MS, Day AJ, Salustri A, Hascall VC, Glant TT, Mikecz K. Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice. Development. 2003;130:2253–61.

    Article  CAS  PubMed  Google Scholar 

  19. Varani S, Elvin JA, Yan C, DeMAyo J, DeMyo FJ, Horton HF, Byrne MC, Matzuk MM. Knockout of pentraxin 3, a downstream target of growth differentiation factor-8, causes female subfertility. Mol Endcrinol. 2002;16:1154–67.

    Article  CAS  Google Scholar 

  20. Bolamba D, Russ KD, Harper SA, Sandler JL, Durrant BS. Effects of epidermal growth factor and hormones on granulose expansion and nuclear maturation of dog oocytes in vitro. Theriogenology. 2006;65:1037–47.

    Article  CAS  PubMed  Google Scholar 

  21. Ohta H, Sato K, Murata N, Damirin A, Malchinkhuu E, Kon J, Kimura T, Tobo M, Yamazaki Y, Watanabe T, Yagi M, Sato M, Suzuki R, Murooka H, Sakai T, Nishitoba T, Im DS, Nochi H, Tamoto K, Tomura H, Okajima F. Ki16425, a subtype-selective antagonist for EDG-family lysophosphatidic acid receptors. Mol Pharmacol. 2003;64:994–1005.

    Article  CAS  PubMed  Google Scholar 

  22. Harris TE, Persaud SJ, Jones PM. Atypical isoforms of PKC and insulin secretion from pancreatic b-cells: evidence using Go 6976 and Ro 31-8220 as PKC inhibitors. Biochem Biophys Res Commun. 1996;1996(227):672–6.

    Article  Google Scholar 

  23. Shimada M, Hernandez-Gonzalez I, Gonzalez-Robayana I, Richard JS. Paracrine and autocrine regulation of epidermal growth factor-like factors in cumulus oocyte complexes and granulose cells: key roles for prostaglandin synthase 2 and progesterone receptor. Mol Endocrinol. 2006;20:1352–65.

    Article  CAS  PubMed  Google Scholar 

  24. Nemková L, Nagyová, Petlach M, Tománek M, Procházka R. Molecular mechanisms of insulin-like growth factor 1 promoted synthesis and retention of hyaluronic acid in porcine oocyte-cumulus complexes. Biol Reprod. 2007;76:1016–24.

    Article  CAS  Google Scholar 

  25. Su YQ, Rubinstein S, Luria A, Lax Y, Breitbart H. Involvement of MEK-mitogen-activated protein kinase activity in cumulus cells is essential for gonadotropin-induced oocyte meiotic resumption and cumulus expansion in the mouse. Biol Reprod. 2001;65:358–65.

    Article  CAS  PubMed  Google Scholar 

  26. Eppig JJ. The relationship between cumulus cell-oocyte coupling, oocyte meiotic maturation, and cumulus expansion. Dev Biol. 1982;89:268–72.

    Article  CAS  PubMed  Google Scholar 

  27. Schroeder AC, Eppig JJ. The developmental capacity of mouse oocytes that matured spontaneously in vitro is normal. Dev Biol. 1984;102:493–7.

    Article  CAS  PubMed  Google Scholar 

  28. Eppig JJ, Wigglesworth K, Chesnel F. Secretion of cumulus expansion enabling factor by mouse oocytes: relationship to oocyte growth and competence to resume meiosis. Dev Biol. 1993;158:400–9.

    Article  CAS  PubMed  Google Scholar 

  29. Diaz FJ, O’Brien MJ, Wigglesworth K, Eppig JJ. The preantral granulosa cell to cumulus cell transition in the mouse ovary: development of competence to undergo expansion. Dev Biol. 2006;299:91–104.

    Article  CAS  PubMed  Google Scholar 

  30. Liu Z, Armant DR. Lysophosphatidic acid regulates murine blastocyst development by transactivation of receptors for heparin-binding EGF-like growth factor. Exp Cell Res. 2004;2004(296):17–326.

    Google Scholar 

  31. Fan HY, Huo LJ, Chen DY, Schatten H, Sun QY. Protein kinase C and mitogen-activated protein kinase cascade in mouse cumulus cells: cross talk and effect on meiotic resumption of oocyte. Biol Reprod. 2004;70:1178–87.

    Article  CAS  PubMed  Google Scholar 

  32. Downs SM, Chen J. EGF-like peptides mediate FSH-induced maturation of cumulus cell-enclosed mouse oocytes. Mol Reprod Dev. 2008;75:105–14.

    Article  CAS  PubMed  Google Scholar 

  33. Eppig JJ. Regulation by sulfated glycosaminoglycanes of the expansion of cumuli oophori isolated from mice. Biol Reprod. 1981;25:559–608.

    Google Scholar 

  34. Downs SM. Specificity of epidermal growth action on maturation of the murine oocyte and cumulus oophorus in vitro. Biol Reprod. 1989;41:371–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are especially grateful to Professor Shuji Yamano for his contribution to this study. Thanks are given to Dr. Hideo Ohta (Kirin Brewery Co.) for kindly providing Ki16425 and to Mariko Neya for preparing the figures. The authors declare that they have no conflict of interest. This work was funded by a grant-in-aid from the Ministry of Education, Culture, Sports, Sciences and Technology of Japan.

Conflict of interest

Akira Tokumura, Emi Kuwahara, Junpei Yamamoto, Yuya Yano, Midori Omura, Akira Kuwahara, Minoru Irahara declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Shomachi, Tokushima, 770-8505, Japan

    Emi Kuwahara, Junpei Yamamoto, Midori Omura & Akira Tokumura

  2. Department of Obstetrics and Gynecology, School of Medicine, Institute of Health Biosciences, University of Tokushima, Kuramoto-cho, Tokushima, 770-8503, Japan

    Yuya Yano, Akira Kuwahara & Minoru Irahara

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  1. Emi Kuwahara
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  2. Junpei Yamamoto
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  7. Akira Tokumura
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Correspondence to Akira Tokumura.

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Kuwahara, E., Yamamoto, J., Yano, Y. et al. Lysophosphatidic acid stimulates hyaluronan production by mouse cumulus–oocyte complexes. Reprod Med Biol 13, 95–102 (2014). https://doi.org/10.1007/s12522-013-0169-6

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  • DOI: https://doi.org/10.1007/s12522-013-0169-6

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