Endometrial CXCL13 expression is cycle regulated in humans and aberrantly expressed in humans and Rhesus macaques with endometriosis

other OA: bronze public-domain-us
AI-generated summary by claude@2026-06, 2026-06-13

This study found that endometrial CXCL13 expression varies cyclically in healthy women but is aberrantly elevated during the proliferative phase in women and macaques with endometriosis.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-06, 2026-06-13 · read from full text

This study assessed whether C-X-C ligand 13 (CXCL13) is regulated across menstrual cycle phases and whether it is altered in endometriosis by measuring endometrial CXCL13 mRNA (real-time RT-PCR and real-time PCR) and protein localization (immunohistochemistry) in normal humans versus biopsy-confirmed stage 1–4 endometriosis. In healthy women, CXCL13 transcripts were minimal in the proliferative phase and maximal in the secretory phase, but in endometriosis the proliferative-phase eutopic endometrial CXCL13 expression was markedly increased in both humans and rhesus macaques with advanced disease, showing cross-species and cross-stage concordance. A key caveat is that the main comparisons focus on eutopic endometrial tissue expression and its cycle-stage pattern, rather than direct functional outcomes of CXCL13. This paper is centrally about endometriosis — it identifies cycle- and disease-associated changes in endometrial CXCL13 expression in human endometriosis and corroborates them in a rhesus macaque model.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

C-X-C ligand 13 (CXCL13), a regulator of mucosal immunity, is secreted by human endometrial epithelium and may be involved in embryo implantation. However, cyclic expression of human endometrial CXCL13 in health and disease is not well studied. This study examines cycle stage-specific endometrial CXCL13 expression in normal humans when compared to those with biopsy-confirmed, stage 1 to 4 endometriosis using real-time reverse transcriptase, real-time polymerase chain reaction and immunohistochemistry. Eutopic endometrial CXCL13 expression was also compared between normal, control Rhesus macaques, and macaques with advanced endometriosis. In healthy women, CXLC13 messenger RNA expression was minimal in the proliferative phase and maximal in the secretory phase. However, in the presence of endometriosis, proliferative-phase endometrial expression markedly increased in both humans and rhesus subjects (P < .05). The cross-species and cross-stage concordance suggests a pathophysiologic role for CXCL13 in endometriosis and its use as a biomarker for disease.
Full text 12,628 characters · extracted from oa-doi-fallback · 2 sections · click to expand

Abstract

C-X-C ligand 13 (CXCL13), a regulator of mucosal immunity, is secreted by human endometrial epithelium and may be involved in embryo implantation. However, cyclic expression of human endometrial CXCL13 in health and disease is not well studied. This study examines cycle stage-specific endometrial CXCL13 expression in normal humans when compared to those with biopsy-confirmed, stage 1 to 4 endometriosis using real-time reverse transcriptase, real-time polymerase chain reaction and immunohistochemistry. Eutopic endometrial CXCL13 expression was also compared between normal, control Rhesus macaques, and macaques with advanced endometriosis. In healthy women, CXLC13 messenger RNA expression was minimal in the proliferative phase and maximal in the secretory phase. However, in the presence of endometriosis, proliferative-phase endometrial expression markedly increased in both humans and rhesus subjects (P < .05). The cross-species and cross-stage concordance suggests a pathophysiologic role for CXCL13 in endometriosis and its use as a biomarker for disease. Similar content being viewed by others

References

D’Hooghe TM, Debrock S, Hill JA, Meuleman C. Endometriosis and subfertility: is the relationship resolved? Semin Reprod Med. 2003;21(2):243–254. Galle PC. Clinical presentation and diagnosis of endometriosis. Obstet Gynecol Clin North Am. 1989;16(1):29–42. Rawson JM. Prevalence of endometriosis in asymptomatic women. J Reprod Med. 1991;36(7):513–515. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012;98(3):591–598. Chand AL, Murray AS, Jones RL, Hannan NJ, Salamonsen LA, Rombauts L. Laser capture microdissection and cDNA array analysis of endometrium identify CCL16 and CCL21 as epithelialderived inflammatory mediators associated with endometriosis. Reprod Biol Endocrinol. 2007;5:18. Ulukus EC, Ulukus M, Seval Y, Zheng W, Arici A. Expression of interleukin-8 and monocyte chemotactic protein-1 in adenomyosis. Hum Reprod. 2005;20(10):2958–2963. Bulun SE, Cheng YH, Yin P, et al. Progesterone resistance in endometriosis: link to failure to metabolize estradiol. Mol Cell Endocrinol. 2006;248(1–2):94–103. Kitawaki J, Kusuki I, Koshiba H, Tsukamoto K, Honjo H. Expression of aromatase cytochrome P450 in eutopic endometrium and its application as a diagnostic test for endometriosis. Gynecol Obstet Invest. 1999;48(suppl 1):21–28. Lessey BA, Castelbaum AJ, Sawin SW, et al. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab. 1994;79(2):643–649. Donaghay M, Lessey BA. Uterine receptivity: alterations associated with benign gynecological disease. Semin Reprod Med. 2007;25(6):461–475. Abushahin F, Goldman KN, Barbieri E, Milad M, Rademaker A, Bulun SE. Aromatase inhibition for refractory endometriosisrelated chronic pelvic pain. Fertil Steril. 2011;96(4):939–942. Kennedy S, Bergqvist A, Chapron C, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005;20(10):2698–2704. Bennett GL, Slywotzky CM, Cantera M, Hecht EM. Unusual manifestations and complications of endometriosis–spectrum of imaging findings: pictorial review. AJR Am J Roentgenol. 2010;194(6 suppl):WS34–WS46. Cheng YM, Wang ST, Chou CY. Serum CA-125 in preoperative patients at high risk for endometriosis. Obstet Gynecol. 2002;99(3):375–380. Mol BW, Bayram N, Lijmer JG, et al. The performance of CA-125 measurement in the detection of endometriosis: a meta-analysis. Fertil Steril. 1998;70(6):1101–1108. Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol. 1984;64(2):151–154. Dmowski WP, Gebel HM, Braun DP. The role of cell-mediated immunity in pathogenesis of endometriosis. Acta Obstet Gynecol Scand Suppl. 1994;159:7–14. Eyster KM, Klinkova O, Kennedy V, Hansen KA. Whole genome deoxyribonucleic acid microarray analysis of gene expression in ectopic versus eutopic endometrium. Fertil Steril. 2007;88(6):1505–1533. Harada T, Iwabe T, Terakawa N. Role of cytokines in endometriosis. Fertil Steril. 2001;76(1):1–10. Oosterlynck DJ, Cornillie FJ, Waer M, Vandeputte M, Koninckx PR. Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium. Fertil Steril. 1991;56(1):45–51. Steele RW, Dmowski WP, Marmer DJ. Immunologic aspects of human endometriosis. Am J Reprod Immunol. 1984;6(1):33–36. Witz CA. Interleukin-6: another piece of the endometriosiscytokine puzzle. Fertil Steril. 2000;73(2):212–214. Boddeke EW. Involvement of chemokines in pain. Eur J Pharmacol. 2001;429(1–3):115–119. Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001;75(1):1–10. Fernandis AZ, Prasad A, Band H, Klosel R, Ganju RK. Regulation of CXCR4-mediated Chemotaxis and chemoinvasion of breast cancer cells. Oncogene. 2004;23(1):157–167. Scotton CJ, Wilson JL, Scott K, et al. Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer. Cancer Res. 2002;62(20):5930–5938. Barcz E, Kaminski P, Marianowski L. Role of cytokines in pathogenesis of endometriosis. Med Sci Monit. 2000;6(5):1042–1046. Garcia-Velasco JA, Arici A. Interleukin-8 stimulates the adhesion of endometrial stromal cells to fibronectin. Fertil Steril. 1999;72(2):336–340. Ansel KM, Harris RB, Cyster JG. CXCL13 is required for B1 cell homing, natural antibody production, and body cavity immunity. Immunity. 2002;16(1):67–76. Dominguez F, Martinez S, Quinonero A, et al. CXCL10 and IL-6 induce Chemotaxis in human trophoblast cell lines. Mol Hum Reprod. 2008;14(7):423–430. Muller G, Hopken UE, Stein H, Lipp M. Systemic immunoregulatory and pathogenic functions of homeostatic chemokine receptors. J Leukoc Biol. 2002;72(1):1–8. Dominguez F, Gadea B, Esteban FJ, Horcajadas JA, Pellicer A, Simon C. Comparative protein-profile analysis of implanted versus non-implanted human blastocysts. Hum Reprod. 2008;23(9):1993–2000. Macklon NS, van der Gaast MH, Hamilton A, Fauser BC, Giudice LC. The impact of ovarian stimulation with recombinant FSH in combination with GnRH antagonist on the endometrial transcriptome in the window of implantation. Reprod Sci. 2008; 15(4):357–365. Talbi S, Hamilton AE, Vo KC, et al. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women. Endocrinology. 2006;147(3):1097–1121. Burney RO, Talbi S, Hamilton AE, et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007;148(8):3814–3826. Bromer JG, Aldad TS, Taylor HS. Defining the proliferative phase endometrial defect. Fertil Steril. 2009;91(3):698–704. Petracco RG, Kong A, Grechukhina O, Krikun G, Taylor HS. Global gene expression profiling of proliferative phase endometrium reveals distinct functional subdivisions. Reprod Sci. 2012;19(10):1138–1145. Houston DE, Noller KL, Melton LJ III, Selwyn BJ, Hardy RJ. Incidence of pelvic endometriosis in Rochester, Minnesota, 1970–1979. Am J Epidemiol. 1987;125(6):959–969. Brenner RM, Slayden OD. Steroid receptors in blood vessels of the rhesus macaque endometrium: a review. Arch Histol Cytol. 2004;67(5):411–416. Slayden OD, Brenner RM. Hormonal regulation and localization of estrogen, progestin and androgen receptors in the endometrium of nonhuman primates: effects of progesterone receptor antagonists. Arch Histol Cytol. 2004;67(5):393–409. Keator CS, Mah K, Ohm L, Slayden OD. Estrogen and progesterone regulate expression of the endothelins in the rhesus macaque endometrium. Hum Reprod. 2011;26(7):1715–1728. Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod. 2002;17(9):2287–2299. Petracco R, Grechukhina O, Popkhadze S, Massasa E, Zhou Y, Taylor HS. MicroRNA 135 regulates HOXA10 expression in endometriosis. J Clin Endocrinol Metab. 2011;96(12):E1925–E1933. Kao LC, Germeyer A, Tulac S, et al. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology. 2003;144(7):2870–2881. Taylor HS, Bagot C, Kardana A, Olive D, Arici A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999;14(5):1328–1331. Legler DF, Loetscher M, Roos RS, Clark-Lewis I, Baggiolini M, Moser B. B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. J Exp Med. 1998;187(4):655–660. Paoletti S, Petkovic V, Sebastiani S, Danelon MG, Uguccioni M, Gerber BO. A rich chemokine environment strongly enhances leukocyte migration and activities. Blood. 2005;105(9):3405–3412. Kowarik MC, Cepok S, Sellner J, et al. CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. J Neuroinflammation. 2012;9:93. Vermi W, Lonardi S, Bosisio D, et al. Identification of CXCL13 as a new marker for follicular dendritic cell sarcoma. J Pathol. 2008;216(3):356–364. Ishikawa S, Matsushima K. Aberrant B1 cell trafficking in a murine model for lupus. Front Biosci. 2007;12:1790–1803. Wong CK, Wong PT, Tam LS, Li EK, Chen DP, Lam CW. Elevated production of B cell chemokine CXCL13 is correlated with systemic lupus erythematosus disease activity. J Clin Immunol. 2010;30(1):45–52. Festa ED, Hankiewicz K, Kim S, et al. Serum levels of CXCL13 are elevated in active multiple sclerosis. Mult Scler. 2009;15(11):1271–1279. Meraouna A, Cizeron-Clairac G, Panse RL, et al. The chemokine CXCL13 is a key molecule in autoimmune myasthenia gravis. Blood. 2006;108(2):432–440. Carlsen HS, Baekkevold ES, Morton HC, Haraldsen G, Brandtzaeg P. Monocyte-like and mature macrophages produce CXCL13 (B cell-attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis. Blood. 2004; 104(10):3021–3027. Meeuwisse CM, van der Linden MP, Rullmann TA, et al. Identification of CXCL13 as a marker for rheumatoid arthritis outcome using an in silico model of the rheumatic joint. Arthritis Rheum. 2011;63(5):1265–1273. Rioja I, Hughes FJ, Sharp CH, et al. Potential novel biomarkers of disease activity in rheumatoid arthritis patients: CXCL13, CCL23, transforming growth factor alpha, tumor necrosis factor receptor superfamily member 9, and macrophage colonystimulating factor. Arthritis Rheum. 2008;58(8):2257–2267. Bianco B, Andre GM, Vilarino FL, et al. The possible role of genetic variants in autoimmune-related genes in the development of endometriosis. Hum Immunol. 2012;73(3):306–315. Olovsson M. Immunological aspects of endometriosis: an update. Am J Reprod Immunol. 2011;66(suppl 1): 101–104. Maybin JA, Critchley HO, Jabbour HN. Inflammatory pathways in endometrial disorders. Mol Cell Endocrinol. 2011;335(1):42–51. Khan KN, Kitajima M, Hiraki K, et al. Immunopathogenesis of pelvic endometriosis: role of hepatocyte growth factor, macrophages and ovarian steroids. Am J Reprod Immunol. 2008;60(5):383–404. Singh S, Singh R, Sharma PK, et al. Serum CXCL13 positively correlates with prostatic disease, prostate-specific antigen and mediates prostate cancer cell invasion, integrin clustering and cell adhesion. Cancer Lett. 2009;283(1):29–35. El Haibi CP, Sharma PK, Singh R, et al. PI3Kp110-, Src-, FAK-dependent and DOCK2-independent migration and invasion of CXCL13-stimulated prostate cancer cells. Mol Cancer. 2010;9:85. Panse J, Friedrichs K, Marx A, et al. Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients. Br J Cancer. 2008;99(6):930–938. Weiss N, Deboux C, Chaverot N, et al. IL8 and CXCL13 are potent chemokines for the recruitment of human neural precursor cells across brain endothelial cells. J Neuroimmunol. 2010;223(1–2):131–134. Louboutin JP, Chekmasova A, Marusich E, Agrawal L, Strayer DS. Role of CCR5 and its ligands in the control of vascular inflammation and leukocyte recruitment required for acute excitotoxic seizure induction and neural damage. FASEB J. 2011;25(2):737–753. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Franasiak, J.M., Burns, K.A., Slayden, O. et al. Endometrial CXCL13 Expression Is Cycle Regulated in Humans and Aberrantly Expressed in Humans and Rhesus Macaques With Endometriosis. Reprod. Sci. 22, 442–451 (2015). https://doi.org/10.1177/1933719114542011 Published: Issue date: DOI: https://doi.org/10.1177/1933719114542011

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

MeSH descriptors

Chemokine CXCL13 Endometriosis Endometrium Menstrual Cycle Animals Biopsy Case-Control Studies Cell Proliferation Chemokine CXCL13 Chemokine CXCL13 Disease Models, Animal Endometriosis Endometriosis Endometriosis Endometriosis Endometrium Endometrium Female Humans Immunohistochemistry

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. The paper's references may be in our DB but unresolved to ``paper_id`` (resolution happens at ingest when the cited DOI matches a row we already have). Run the cross-source citation reconcile pass to retry.

Source provenance

europepmc
last seen: 2026-06-16T06:07:01.518242+00:00
pubmed
last seen: 2026-05-13T22:18:22.440000+00:00
unpaywall
last seen: 2026-05-14T19:30:52.867331+00:00
License: public-domain-us · commercial use OK · attribution required
Courtesy of the U.S. National Library of Medicine