Skip to main content
Log in

The Hyaluronic Acid System is Intact in Menstrual Endometrial Cells in Women With and Without Endometriosis

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Objective

To characterize the production and degradation of hyaluronic acid (HA) in menstrual endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs) in women with and without endometriosis. To identify the presence of CD44, the primary receptor of HA, in menstrual EECs and ESCs in women with and without endometriosis.

Design

In vitro study.

Setting

Academic center.

Patient(s)

Deidentified patient samples from women with and without endometriosis.

Interventions

EECs and ESCs were isolated from menstrual endometrial biopsies performed on women with (N = 9) and without (N = 11) endometriosis confirmed by laparoscopy. Main Outcome Measure: Real-time polymerase chain reaction, Western blot, and immunohistochemistry were used to assess hyaluronic acid synthase (HAS) isoforms 1, 2, and 3; hyaluronidase (HYAL) isoforms 1 and 2; and standard CD44. Student t test was used to analyze the results.

Results

There was no significant difference in messenger RNA (mRNA) or protein expression of HAS2, HAS3, HYAL1, or HYAL2 in EECs or ESCs from women with or without endometriosis. HAS1 mRNA was variably detected, whereas HAS1 protein was similarly expressed in EECs and ESCs from women with and without endometriosis. Standard CD44 was expressed in both cell types, and expression did not differ in cells from women with or without endometriosis.

Conclusions

The HA system is expressed in eutopic menstrual ESCs and EECs from women with and without endometriosis. There are no differences in expression in HA production or degradation enzymes in EECs or ESCs from women with and without endometriosis. Standard CD44 expression does not differ in eutopic menstrual endometrial cells from women with and without endometriosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Wheeler JM. Epidemiology of endometriosis-associated infertility. J Reprod Med. 1989;34(1):41–46.

    CAS  PubMed  Google Scholar 

  2. Simoens S, Dunselman G, Dirksen C, et al. The burden of endo-metriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod (Oxford, England). 2012;27(5):1292–1299.

    Google Scholar 

  3. Bulun SE. Endometriosis. New Engl J Med. 2009;360(3): 268–279.

    CAS  PubMed  Google Scholar 

  4. Siiskonen H, Karna R, Hyttinen JM, Tammi RH, Tammi MI, Rilla K. Hyaluronan synthase 1 (HAS1) produces a cytokine-and glucose-inducible, CD44-dependent cell surface coat. Exp Cell Res. 2014;320(1):153–163.

    CAS  PubMed  Google Scholar 

  5. Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990;61(7):1303–1313.

    CAS  PubMed  Google Scholar 

  6. Hasegawa A, Yoshino O, Osuga Y, et al. Hyaluronic acid reagent suppressed endometriotic lesion formation in a mouse model. Fertil Steril. 2010;93(8):2757–2759.

    CAS  PubMed  Google Scholar 

  7. Knudtson JF, Tekmal RR, Santos MT, et al. Impaired development of early endometriotic lesions in CD44 knockout mice. Reprod Sci (Thousand Oaks, Calif.). 2016;23(1):87–91.

    Google Scholar 

  8. Dechaud H, Witz CA, Montoya-Rodriguez IA, Degraffenreid LA, Schenken RS. Mesothelial cell-associated hyaluronic acid promotes adhesion of endometrial cells to mesothelium. Fertil Steril. 2001;76(5):1012–1018.

    CAS  PubMed  Google Scholar 

  9. Nykopp TK, Rilla K, Tammi MI, et al. Hyaluronan synthases (HAS1–3) and hyaluronidases (HYAL1–2) in the accumulation of hyaluronan in endometrioid endometrial carcinoma. BMC Cancer. 2010;10:512.

    PubMed  PubMed Central  Google Scholar 

  10. Auvinen P, Rilla K, Tumelius R, et al. Hyaluronan synthases (HAS1–3) in stromal and malignant cells correlate with breast cancer grade and predict patient survival. Breast Cancer Res Treat. 2014;143(2):277–286.

    CAS  PubMed  Google Scholar 

  11. Paiva P, van Damme MP, Tellbach M, Jones RL, Jobling T, Salamonsen LA. Expression patterns of hyaluronan, hyaluronan synthases and hyaluronidases indicate a role for hyaluronan in the progression of endometrial cancer. Gynecol Oncol. 2005;98(2): 193–202.

    CAS  PubMed  Google Scholar 

  12. Nykopp TK, Pasonen-Seppanen S, Tammi MI, et al. Decreased hyaluronidase 1 expression is associated with early disease recur-rence in human endometrial cancer. Gynecol Oncol. 2015;137(1): 152–159.

    CAS  PubMed  Google Scholar 

  13. Rodgers AK, Nair A, Binkley PA, Tekmal R, Schenken RS. Inhi-bition of CD44 N- and O-linked glycosylation decreases endome-trial cell lines attachment to peritoneal mesothelial cells. Fertil Steril. 2011;95(2):823–825.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Griffith JS, Liu YG, Tekmal RR, Binkley PA, Holden AE, Schenken RS. Menstrual endometrial cells from women with endome-triosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants. Fertil Steril. 2010;93(6):1745–1749.

    CAS  PubMed  Google Scholar 

  15. Nair HB, Luthra R, Kirma N, et al. Induction of aromatase expression in cervical carcinomas: effects of endogenous estrogen on cervical cancer cell proliferation. Cancer Res. 2005;65(23): 11164–11173.

    CAS  PubMed  Google Scholar 

  16. Tekmal RR, Liu YG, Nair HB, et al. Estrogen receptor alpha is required for mammary development and the induction of mammary hyperplasia and epigenetic alterations in the aromatase transgenic mice. J Steroid Biochem Mol Biol. 2005;95(1–5):9–15.

    CAS  PubMed  Google Scholar 

  17. Sun M, Ramirez M, Challis JR, Gibb W. Immunohistochemical localization of the glucocorticoid receptor in human fetal membranes and decidua at term and preterm delivery. J Endocrinol. 1996;149(2):243–248.

    CAS  PubMed  Google Scholar 

  18. Knudtson JF, Tekmal RR, Santos MT, et al. Impaired development of early endometriotic lesions in CD44 knockout mice. Reprod Sci (Thousand Oaks, Calif.). 2016;23(1):87–91.

    Google Scholar 

  19. Siiskonen H, Oikari S, Pasonen-Seppanen S, Rilla K. Hyaluronan synthase 1: a mysterious enzyme with unexpected functions. Front Immunol. 2015;6:43.

    PubMed  PubMed Central  Google Scholar 

  20. Rilla K, Oikari S, Jokela TA, et al. Hyaluronan synthase 1 (HAS1) requires higher cellular UDP-GlcNAc concentration than HAS2 and HAS3. J Biol Chem. 2013;288(8):5973–5983.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Csoka AB, Frost GI, Stern R. The six hyaluronidase-like genes in the human and mouse genomes. Matrix Biol. 2001;20(8): 499–508.

    CAS  PubMed  Google Scholar 

  22. Ripellino JA, Klinger MM, Margolis RU, Margolis RK. The hyaluronic acid binding region as a specific probe for the localization of hyaluronic acid in tissue sections. Application to chick embryo and rat brain. J Histochem Cytochem. 1985;33(10):1060–1066.

    CAS  PubMed  Google Scholar 

  23. Shibutani T, Imai K, Kanazawa A, Iwayama Y. Use of hyaluronic acid binding protein for detection of hyaluronan in ligature-induced periodontitis tissue. J Periodontal Res. 1998;33(5): 265–273.

    CAS  PubMed  Google Scholar 

  24. Cyphert JM, Trempus CS, Garantziotis S. Size matters: molecular weight specificity of hyaluronan effects in cell biology. Int J Cell Biol. 2015;2015:563818.

    PubMed  PubMed Central  Google Scholar 

  25. Shinohara T, Izawa T, Mino-Oka A, et al. Hyaluronan metabolism in overloaded temporomandibular joint. J Oral Rehabil. 2016; 43(12):921–928.

    CAS  PubMed  Google Scholar 

  26. Koo YH, Na YJ, Ahn MY, Jeon HN, Yeom JI, Lee KS. Expression of CD44 in endometrial stromal cells from women with and without endometriosis and its effect on the adherence to peritoneal mesothelial cells. Obstet Gynecol Sci. 2013;56(2):102–109.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jennifer F. Knudtson MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Knudtson, J.F., McLaughlin, J.E., Santos, M.T. et al. The Hyaluronic Acid System is Intact in Menstrual Endometrial Cells in Women With and Without Endometriosis. Reprod. Sci. 26, 109–113 (2019). https://doi.org/10.1177/1933719118766257

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719118766257

Keywords

Navigation