Impaired Development of Early Endometriotic Lesions in CD44 Knockout Mice

Previous studies have shown endometrial cell (EC) CD44 and peritoneal mesothelial cell (PMC)-associated hyaluronan (hyaluronic acid [HA]) are involved in the attachment of endometrial stroma and epithelial cells to peritoneal mesothelium. Here we assess the CD44–HA interaction in the formation of the early endometriotic lesion using CD44–/– (knockout) mice. Using an established murine model and crossover technique, endometrial tissue from donor mice (wild type [WT] and CD44–/–) was used to induce endometriosis in recipient mice (WT and CD44–/–). Endometriotic lesions were visualized by fluorescent microscopy and confirmed by hematoxylin and eosin staining. Early endometriotic lesions were decreased when CD44–/– endometrium was placed in WT recipients and when WT endometrium was placed in CD44–/– recipients (P = .002). Early endometriotic lesions were also significantly decreased when both peritoneal and endometrial tissues lacked CD44 expression (P < .01). These studies demonstrate that both EC and PMC CD44 play a role in the development of early endometriotic lesion. Similar content being viewed by others

Wheeler JM. Epidemiology of endometriosis-associated infertility. J Reprod Med. 1989;34(1):41–46. Velebil P, Wingo PA, Xia Z, Wilcox LS, Peterson HB. Rate of hospitalization for gynecologic disorders among reproductive-age women in the United States. Obstet Gynecol. 1995;86(5):764–769. Witz CA, Schenken RS. Pathogenesis. Semin Reprod Endocrinol. 1997;15(3):199–208. Machado DE, Palumbo A Jr, Santos JM, et al. A GFP endometriosis model reveals important morphological characteristics of the angiogenic process that govern benign and malignant diseases. Histol Histopathol. 2014;29(7):903–912. Groothuis PG, Koks CA, de Goeij AF, Dunselman GA, Arends JW, Evers JL. Adhesion of human endometrium to the epithelial lining and extracellular matrix of amnion in vitro: an electron microscopic study. Human Reprod (Oxford, England). 1998;13(8):2275–2281. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279. Nagano O, Saya H. Mechanism and biological significance of CD44 cleavage. Cancer Sci. 2004;95(12):930–935. Behzad F, Seif MW, Campbell S, Aplin JD. Expression of two isoforms of CD44 in human endometrium. Biol Reprod. 1994;51(4):739–747. Borland G, Ross JA, Guy K. Forms and functions of CD44. Immunology. 1998;93(2):139–148. Nishimura S, Chung YS, Yashiro M, Inoue T, Sowa M. CD44H plays an important role in peritoneal dissemination of scirrhous gastric cancer cells. Jpn J Cancer Res. 1996;87(12):1235–1244. Lessan K, Aguiar DJ, Oegema T, Siebenson L, Skubitz AP. CD44 and beta1 integrin mediate ovarian carcinoma cell adhesion to peritoneal mesothelial cells. Am J Pathol. 1999;154(5):1525–1537. 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. Rodgers AK, Nair A, Binkley PA, Tekmal R, Schenken RS. Inhibition of CD44 N- and O-linked glycosylation decreases endometrial cell lines attachment to peritoneal mesothelial cells. Fertil Steril. 2011;95(2):823–825. Griffith JS, Liu YG, Tekmal RR, Binkley PA, Holden AE, Schenken RS. Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants. Fertil Steril. 2010;93(6):1745–1749. Jensen JR, Witz CA, Schenken RS, Tekmal RR. A potential role for colony-stimulating factor 1 in the genesis of the early endometriotic lesion. Fertil Steril. 2010;93(1):251–256. Schmits R, Filmus J, Gerwin N, et al. CD44 regulates hematopoietic progenitor distribution, granuloma formation, and tumorigenicity. Blood. 1997;90(6):2217–2233. Protin U, Schweighoffer T, Jochum W, Hilberg F. CD44-deficient mice develop normally with changes in subpopulations and recirculation of lymphocyte subsets. J Immunol (Baltimore, Md.:1950). 1999;163(9):4917–4923. 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. Raheem KA, Marei WF, Mifsud K, Khalid M, Wathes DC, Fouladi-Nashta AA. Regulation of the hyaluronan system in ovine endometrium by ovarian steroids. Reprod (Cambridge, England). 2013;145(5):491–504. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Knudtson, J.F., Tekmal, R.R., Santos, M.T. et al. Impaired Development of Early Endometriotic Lesions in CD44 Knockout Mice. Reprod. Sci. 23, 87–91 (2016). https://doi.org/10.1177/1933719115594022 Published: Issue date: DOI: https://doi.org/10.1177/1933719115594022