Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2012

Open Access 01-12-2012 | Research

Expression of the T regulatory cell transcription factor FoxP3 in peri-implantation phase endometrium in infertile women with endometriosis

Authors: Shufang Chen, Jian Zhang, Changxiao Huang, Wen Lu, Yan Liang, Xiaoping Wan

Published in: Reproductive Biology and Endocrinology | Issue 1/2012

Login to get access

Abstract

Background

Endometriosis (EM) is highly associated with infertility. The precise mechanism underlying EM-associated infertility remains controversial. This study aimed to investigate the pathogenesis of infertility in women with EM by comparing FoxP3+ T regulatory cells (Tregs) expression in the eutopic endometrium of infertile women with EM and endometrium from healthy fertile women.

Methods

As a marker of Tregs, FoxP3 expression was analyzed in eutopic endometrium during the peri-implantation phase in infertile women with mild EM (n = 7), advanced EM (n = 20), and normally fertile women without EM (n = 20). FoxP3 mRNA expression was analyzed by quantitative real-time RT-PCR. FoxP3 protein expression was assessed by immunohistochemistry.

Results

FoxP3 mRNA expression in all infertile patients with EM was significantly higher than the control group (P < 0.05) by non-parametric Mann–Whitney U-test. Further analysis based on the extent of EM revealed that FoxP3 mRNA expression in infertile patients with advanced EM was significantly higher than the mild EM group and the control group (P < 0.05). Immunohistochemistry analysis showed predominant positive staining for FoxP3 protein in the endometrial stroma. In addition, the number of FoxP3+ cells in the eutopic endometrium of infertile women with advanced EM was marginally higher than the mild EM group and the control group, although the differences were not statistically significant (P > 0.05) by two-tailed t-tests.

Conclusions

These findings suggest that FoxP3+ Tregs in the peri-implantation endometrium might participate in the pathogenesis of advanced EM. However, they are not directly involved in the pathogenesis of advanced EM associated with infertility. The differential expression of FoxP3 in infertile women with mild EM and advanced EM implicates that notable differences in the uterine immune status are likely involved in the pathogenesis of mild EM associated with infertility in the peri-implantation endometrium.
Appendix
Available only for authorised users
Literature
1.
2.
Ulukus M, Cakmak H, Arici A: The role of endometrium in endometriosis. J Soc Gynecol Investig. 2006, 13: 467-476.PubMed
3.
Simo’n C, Gutie’rrez A, Vidal A, de los Santos MJ, Tari’n JJ, Remohi’ J, Pellicer A: Outcome of patients with endometriosis in assisted reproduction: results from in vitro fertilization and oocyte donation. Hum Reprod. 1994, 9: 725-729.
4.
Klemmt PA, Carver JG, Kennedy SH, Koninckx PR, Mardon HJ: Stromal cells from endometriotic lesions and endometrium from women with endometriosis have reduced decidualization capacity. Fertil Steril. 2006, 85: 564-572. 10.1016/j.fertnstert.2005.08.046.PubMedCentralCrossRefPubMed
5.
Li XC, Turka LA: An update on regulatory T cells in transplant tolerance and rejection. Nat Rev Nephrol. 2010, 6: 577-583. 10.1038/nrneph.2010.101.CrossRefPubMed
6.
Guerin LR, Prins JR, Robertson SA: Regulatory T cells and immune tolerance in pregnancy: a new target for infertility treatment?. Hum Reprod Update. 2009, 15: 517-535. 10.1093/humupd/dmp004.PubMedCentralCrossRefPubMed
7.
Yang H, Qiu L, Chen G, Ye Z, Lu C, Lin Q: Proportional change of CD4+CD25+ regulatory T cells in decidua and peripheral blood in unexplained recurrent spontaneous abortion patients. Fertil Steril. 2008, 89: 656-661. 10.1016/j.fertnstert.2007.03.037.CrossRefPubMed
8.
Jasper MJ, Tremellen KP, Robertson SA: Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Mol Hum Reprod. 2006, 12: 301-308. 10.1093/molehr/gal032.CrossRefPubMed
9.
Berbic M, Hey-Cunningham AJ, Ng C, Tokushige N, Ganewatta S, Markham R: The role of Foxp3+ regulatory T-cells in endometriosis: a potential controlling mechanism for a complex, chronic immunological condition. Hum Reprod. 2010, 25: 900-907. 10.1093/humrep/deq020.CrossRefPubMed
10.
Noyes RW, Hertig AT, Rock J: Dating the endometrial biopsy. Am J Obstet Gynecol. 1975, 122: 262-263.PubMed
11.
Canis M, Donnez JG, Guzick DS, Halme JK, Rock JA, Schenken RS, Vernon MW: Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril. 1997, 67: 817-821. 10.1016/S0015-0282(97)81391-X.CrossRef
12.
Donaghay M, Lessey BA: Uterine receptivity: alterations associated with benign gynecological disease. Semin Reprod Med. 2007, 25: 461-475. 10.1055/s-2007-991044.CrossRefPubMed
13.
Barnhart K, Dunsmoor-Su R, Coutifaris C: Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002, 77: 1148-1155. 10.1016/S0015-0282(02)03112-6.CrossRefPubMed
14.
Burney RO, Talbi S, Hamilton AE, Vo KC, Nyegaard M, Nezhat CR: Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007, 148: 3814-3826. 10.1210/en.2006-1692.CrossRefPubMed
15.
Carson DD, Bagchi I, Dey SK, Enders AC, Fazleabas AT, Lessey BA: Embryo implantation. Dev Biol. 2000, 223: 217-237. 10.1006/dbio.2000.9767.CrossRefPubMed
16.
Norwitz ER, Schust DJ, Fisher SJ: Implantation and the survival of early pregnancy. N Engl J Med. 2001, 345: 1400-1408. 10.1056/NEJMra000763.CrossRefPubMed
17.
Van Mourik MS, Macklon NS, Heijnen CJ: Embryonic implantation: cytokines, adhesion molecules, and immune cells in establishing an implantation environment. J Leukoc Biol. 2009, 85: 4-19.CrossRefPubMed
18.
Dosiou C, Giudice LC: Natural killer cells in pregnancy and recurrent pregnancy loss: endocrine and immunologic perspectives. Endocr Rev. 2005, 26: 44-62. 10.1210/er.2003-0021.CrossRefPubMed
19.
Abrahams VM, Kim YM, Straszewski SL, Romero R, Mor G: Macrophages and apoptotic cell clearance during pregnancy. Am J Reprod Immunol. 2004, 51: 275-282. 10.1111/j.1600-0897.2004.00156.x.CrossRefPubMed
20.
Lea RG, Sandra O: Immunoendocrine aspects of endometrial function and implantation. Reproduction. 2007, 134: 389-404. 10.1530/REP-07-0167.CrossRefPubMed
21.
Arruvito L, Sanz M, Banham AH, Fainboim L: Expansion of CD4+CD25+and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction. J Immunol. 2007, 178: 2572-2578.CrossRefPubMed
22.
Berbic M, Fraser IS: Regulatory T cells and other leukocytes in the pathogenesis of endometriosis. J Reprod Immunol. 2011, 88: 149-155. 10.1016/j.jri.2010.11.004.CrossRefPubMed
23.
Basta P, Majka M, Jozwicki W, Lukaszewska E, Knafel A, Grabiec M, Stasienko E, Wicherek L: The frequency of CD25+CD4+ and FOXP3+ regulatory T cells in ectopic endometrium and ectopic decidua. Reprod Biol Endocrinol. 2010, 5: 116-CrossRef
24.
André GM, Barbosa CP, Teles JS, Vilarino FL, Christofolini DM, Bianco B: Analysis of FOXP3 polymorphisms in infertile women with and without endometriosis. Fertil Steril. 2011, 95: 2223-2227. 10.1016/j.fertnstert.2011.03.033.CrossRefPubMed
25.
Prieto GA: Progression of endometriosis to cancer: too MUCh FoxP3+ regulatory T-cell response?. Dis Model Mech. 2011, 4 (2): 139-140. 10.1242/dmm.007278.PubMedCentralCrossRefPubMed
26.
Moldenhauer LM, Diener KR, Thring DM, Brown MP, Hayball JD, Robertson SA: Cross-presentation of male seminal fluid antigens elicits T cell activation to initiate the female immune response to pregnancy. J Immunol. 2009, 182: 8080-8093. 10.4049/jimmunol.0804018.CrossRefPubMed
27.
Robertson SA, Guerin LR, Bromfield JJ, Branson KM, Ahlstrom AC, Care AS: Seminal fluid drives expansion of the CD4+CD25+ T regulatory cell pool and induces tolerance to paternal alloantigens in mice. Biol Reprod. 2009, 80: 1036-1045. 10.1095/biolreprod.108.074658.PubMedCentralCrossRefPubMed
Metadata
Title
Expression of the T regulatory cell transcription factor FoxP3 in peri-implantation phase endometrium in infertile women with endometriosis
Authors
Shufang Chen
Jian Zhang
Changxiao Huang
Wen Lu
Yan Liang
Xiaoping Wan
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2012
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-10-34

Other articles of this Issue 1/2012

Reproductive Biology and Endocrinology 1/2012 Go to the issue

Research

Bovine trophoblastic cell differentiation and binucleation involves enhanced endogenous retrovirus element expression

Research

Vitrification of immature bovine cumulus-oocyte complexes: effects of cryoprotectants, the vitrification procedure and warming time on cleavage and embryo development

Research

Effect of hCG priming on embryonic development of immature oocytes collected from unstimulated women with polycystic ovarian syndrome

Research

Increased expression of kisspeptin and GnRH forms in the brain of scombroid fish during final ovarian maturation and ovulation

Research

Improvement of ovarian response and oocyte quality of aged female by administration of bone morphogenetic protein-6 in a mouse model

Research

Bone morphogenetic protein-15 in follicle fluid combined with age may differentiate between successful and unsuccessful poor ovarian responders