Analysis of point mutations in interleukin-11 gene in the population of infertile patients and fertile control women


Authors: P. Lhotská 1,2;  P. Martínek 1;  M. Čedíková 1,2;  P. Lošan 1;  M. Králíčková 1,2,3;  V. Kališ 3;  Z. Novotný 3
Authors‘ workplace: Ústav histologie a embryologie LF UK, Plzeň, přednostka doc. MUDr. M. Králíčková, Ph. D. 1;  Biomedicínské centrum LF UK, Plzeň, vědecký ředitel doc. MUDr. M. Štengl, Ph. D. 2;  Gynekologicko-porodnická klinika LF UK a FN, Plzeň, přednosta doc. MUDr. Z. Novotný, CSc. 3
Published in: Ceska Gynekol 2014; 79(1): 48-52

Overview

Objective:
The interleukin-11 (IL-11) is one of the most important signaling factors in the process of decidua-lization and embryo-maternal cross talk during the embryo implantation. We investigated the prevalence of the IL-11 gene point variants in the population of infertile women and fertile control subjects.

Design:
A cohort study.

Setting:
Department of Obstetrics and Gynecology, Faculty of Medicine and University Hospital of Charles University, Pilsen.

Subjects and methods:
The population to screen consisted of 354 infertile women. The control population was comprised of 195 healthy fertile subjects. For the mutational analysis, the temperature gradient gel electrophoresis (TGGE) and direct sequencing had been used. The groups of fertile controls and infertile patients were compared for statistically significant difference using the Fisher´s 2 by 2 Exact test.

Results:
Thirteen potentially functional IL-11 gene variants, the G to A transversions at the position 3651 (G3651A) leading to the arginin to histidin exchange on the position 113 (R113H) were detected in the group of infertile women. No mutations were identified in the control group, which means that the frequency of functionally relevant mutations of the IL-11 gene in infertile women is significantly enhanced in comparison with controls (p = 0.01, Fisher´s 2 by 2 Exact test).

Conclusion:
The results prove the presence of the potentially functionally relevant IL-11 gene variants in the population of infertile women. The presence of variants does not have to lead directly to decrease fertility but may contribute to the dysbalance of cytokine milieu which is needed for the decidualization as well as subsequent embryo implantation. Even thought IL-11 gene variants occur infrequently, their impact on molecular events during early phases of pregnancy should be further elucidated.

Keywords:
interleukin-11 – variant – decidualization – embryo implantation – infertility – assisted reproduction – in vitro fertilization – temperature gradient gel electrophoresis – DNA sequencing


Sources

1. Balakrishnan, L., Soman, S., Patil, YB., et al. IL-11/IL11RA receptor mediated signaling: a web accessible knowledgebase. Cell Commun Adhes, 2013, 20, 3–4, p. 81–86.

2. Beranová, M., Oliveira, LM., Bedecarrats, GY., et al. Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab, 2001, 86, 4, p. 1580–1588.

3. Carp, H. Cytokines in recurrent miscarriage. Lupus., 2004, 13, 9, p. 630–634.

4. Cork, BA., Li, TC., Warren, MA., Laird, MS. Interleukin-11 in human endometrium: expression throughout the menstrual cycle and the effects of cytokines on endometrial IL-11 production in vitro. J Reprod Imunol, 2001, 50, p. 3–17.

5. Dimitriadis, E., Sharkey, AM., Tan, YL., et al. Immuno-localisation of phosphorylated STAT3, interleukin-11 and leukaemia inhibitory factor in endometrium of women with unexplained infertility during the implantation window. Reprod Biol Endocrinol, 2007, 29, 5, p. 44.

6. Du, XX., Wiliams, DA. Interleukin-11: a multifunctional growth factor derived from the haemopoietic microenvironment. Blood, 1994, 83, 8, p. 2023–2030.

7. Granot, I., Gnainsky, Y., Dekel, N. Endometrial inflammation and effect on implantation improvement and pregnancy outcome. Reproduction, 2012, 144, 6, p. 661–668.

8. Králíčková, M., Šíma, R., Vaněček, T., et al. Leukemia inhibitory factor gene mutations in the population of infertile women are not restricted to nulligravid patients. Eur J Obstet Gynecol Reprod Biol, 2006, 127, 2, p. 231–235.

9. Linjawi, S., Li, TC., Tuckerman, EM., et al. Expression of interleukin-11 receptor alpha and interleukin-11 protein in the endometrium of normal fertile women and women with recurrent miscarriage. J Reprod Immunol, 2004, 64, 1–2, p. 145–155.

10. Robb, L., Li, R., Hartley, L., et al. Infertility in female mice lacking the receptor for interleukin 11 is due to defective uterine response to implantation. Nat Med, 1998, 4, 3, p. 303–308.

11. Sullivan, EA., Zegers-Hochschild, F., Mansour, R., et al. International Committee for Monitoring Assisted Reproductive Technologies (ICMART) world report: assisted reproductive technology 2004. Hum Reprod, 2013, 28, 5, p. 1375–1390.

Labels
Paediatric gynaecology Gynaecology and obstetrics Reproduction medicine

Article was published in

Czech Gynaecology

Issue 1

2014 Issue 1

Most read in this issue
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account