Expression of the anti-Müllerian hormone receptor (AMHR2) in the endometrium of patients with uterine anomalies

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

BACKGROUND: Uterine anomalies are a cause of female reproductive failure. Originally, malformations of the Müllerian ducts are believed to be the main reason for uterus abnormalities. There is an assumption that anti-Müllerian hormone (AMH) or AMH receptor (AMHR2) gene mutation may lead to alterations in the formation of the Müllerian ducts in female fetuses resulting in uterine anomalies.

AIM: The aim of this study was to assess the AMHR2 expression in the endometrium of patients with uterine anomalies and a history of reproductive failure.

MATERIALS AND METHODS: The present study included 112 women, of whom 92 patients were diagnosed with uterine anomalies (main groups): arcuate uterus (n = 30), septated uterus (n = 30), bicornuate uterus (n = 12), unicornuate uterus (n = 10), didelphys uterus (n = 10); and 20 patients had normal uterine anatomy (control group), with the secretory phase (n = 10) and the proliferative phase (n = 10) of menstrual cycle evaluated. Histological and immunohistochemical studies of the endometrium were carried out according to the standard technique with an assessment of AMHR2 marker expression in the biopsy samples.

RESULTS: The AMHR2 area expression in the endometrial stroma was significantly lower in patients with septated uterus compared to those with arcuate uterus (р < 0.001). The same tendency was noted when compared to other uterine anomalies and healthy controls. AMHR2 expression in the endometrial stroma of patients with arcuate uterus was significantly higher compared to unicornuate uterus (p < 0.05).

CONCLUSIONS: The data obtained suggest that morphofunctional characteristics of the endometrium in patients with uterine anomalies have no specific pathognomonic features. The decline in AMHR2 expression in the endometrial stroma seems to be related to chronic endometritis, as an inverse correlation exists between the AMHR2 area expression and chronic endometritis, compromising pregnancy occurrence.

Full Text

Restricted Access

About the authors

Ekaterina V. Kazantseva

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Author for correspondence.
Email: katrin8505@yandex.ru
ORCID iD: 0000-0003-4948-4125
Russian Federation, Saint Petersburg

Gulrukhsor Kh. Tolibova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; North-Western State Medical University named after I.I. Mechnikov

Email: gulyatolibova@yandex.ru
ORCID iD: 0000-0002-6216-6220
SPIN-code: 7544-4825
Scopus Author ID: 23111355700
ResearcherId: Y-6671-2018

MD, Dr. Sci. (Med.)

Russian Federation, Saint Petersburg

Tatyana G. Tral

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; Saint Petersburg State Pediatric Medical University

Email: ttg.tral@yandex.ru
ORCID iD: 0000-0001-8948-4811
SPIN-code: 1244-9631
Scopus Author ID: 37666260400

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Igor Yu. Kogan

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: ikogan@mail.ru
ORCID iD: 0000-0002-7351-6900
SPIN-code: 6572-6450
Scopus Author ID: 56895765600

MD, Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences

Russian Federation, Saint Petersburg

References

  1. Ludwin A, Ludwin I, Kudla M, Kottner J. Reliability of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy and American Society for Reproductive Medicine classification systems for congenital uterine anomalies detected using three-dimensional ultrasonography. Fertil Steril. 2015;104(3):688−697.e8. doi: 10.1016/j.fertnstert.2015.06.019
  2. Grimbizis GF, Gordts S, Di Spiezio Sardo A, et al. The ESHRE-ESGE consensus on the classification of female genital tract congenital anomalies. Gynecol Surg. 2013;10(3):199−212. doi: 10.1007/s10397-013-0800-x
  3. Adamyan LV, Hashukoeva AZ, Kulakov VI. Poroki razvitiya matki i vlagalischa. Moscow: Medicina; 1998. (In Russ.)
  4. Safronov OV, Briukhina EV, Ishchenko LS, et al. Current classification systems and methodological approaches in the diagnosis of uterine malformations. Obstetrics and Gynegology. 2019;(3):18−24. (In Russ.). doi: 10.18565/aig.2019.3.18-24
  5. Kozachenko IF, Arakelyan AS, Smolnikova VYu, Adamyan LV. The role of minimally invasive intrauterine interventions in increasing the effectiveness of IVF programs. Obstetrics and Gynegology. 2020;(9):97−104. (In Russ.). doi: 10.18565/aig.2020.9.97-104
  6. Lekovich J, Stewart J, Anderson S, et al. Placental malperfusion as a possible mechanism of preterm birth in patients with Müllerian anomalies. J Perinat Med. 2017;45(1):45−49. doi: 10.1515/jpm-2016-0075
  7. Abrao MS, Muzii L, Marana R. Anatomical causes of female infertility and their management. Int J Gynecol Obstet. 2013;123(2):18−24. doi: 10.1016/j.ijgo.2013.09.008
  8. Lin K, Zhu X, Xu H, et al. Reproductive outcome following resectoscope metroplasty in women having a complete uterine septum with double cervix and vagina. Int J Gynaecol Obstet. 2009;105(1):25−28. doi: 10.1016/j.ijgo.2008.11.018
  9. Sidel’nikova VM. Nevynashivanie beremennosti – sovremennyj vzgljad na problemu. Akusherstvo i ginekologija. 2007;(5):24−27. (In Russ.)
  10. Rackow BW, Arici A. Reproductive performance of women with müllerian anomalies. Curr Opin Obstet Gynecol. 2007;19(3):229−237. doi: 10.1097/GCO.0b013e32814b0649
  11. Fedele L, Bianchi S, Frontino G. Septums and synechiae: approaches to surgical correction. Clin Obstet Gynecol. 2006;19(49):767−788. doi: 10.1097/01.grf.0000211948.36465.a6
  12. Bhagavath B, Ellie G, Griffiths KM, et al. Uterine malformations: An update of diagnosis, management, and outcomes. Obstet Gynecol Surv. 2017;72(6):377−392. doi: 10.1097/OGX.0000000000000444
  13. Passos IMPE, Britto RL. Diagnosis and treatment of müllerian malformations. Taiwan J Obstet Gynecol. 2020;59(2):183−188. doi: 10.1016/j.tjog.2020.01.003
  14. Devi Wold AS, Pham N, Arici A. Anatomic factors in recurrent pregnancy loss. Semin Reprod Med. 2006;24(1):25−32. doi: 10.1055/s-2006-931798
  15. Surrey ES, Katz-Jaffe MG, Surrey RL, et al. Arcuate uterus: is there an impact on in vitro fertilization outcomes after euploid embryo transfer? Fertil Steril. 2018;109(4):638−643. doi: 10.1016/j.fertnstert.2017.12.001
  16. Robbins JB, Broadwell C, Chow LC, et al. Müllerian duct anomalies: embryological development, classification, and MRI assessment. J Magn Reson Imaging. 2015;41(1):1−12. doi: 10.1002/jmri.24771
  17. Ustinkina TI, Shustov SB. Antimyullerov gormon v diffirincirovke, razvitii i funkcii reproduktivnoi sistemi. Problemi endokrinologii. 2011;(6):39−44. (In Russ.). doi: 10.14341/probl201157639-44
  18. Namkung G, Song JY, Jo HH, et al. Müllerian inhibiting substance induces apoptosis of human endometrial stromal cells in endometriosis. J Clin Endocrinol Metab. 2012;97(9):3224–3230. doi: 10.1210/jc.2012-1538
  19. Shi YG, Massagué J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell. 2003;113(6):685−700. doi: 10.1016/s0092-8674(03)00432-x
  20. Josso N, Belville C, di Clemente N, Picard JY. AMH and AMH receptor defects in persistent Mullerian duct syndrome. Hum Reprod Update. 2005;11(4):351−356. doi: 10.1093/humupd/dmi014
  21. Imbeaud S, Faure E, Lamarre I, et al. Insensitivity to anti-müllerian hormone due to a mutation in the human anti-müllerian hormone receptor. Nat Genet. 1995;11(4):382–388. doi: 10.1038/ng1295-382
  22. Knebelmann B, Boussin L, Guerrier D, et al. Anti-Müllerian hormone Bruxelles: a nonsense mutation associated with the persistent Müllerian duct syndrome. Proc Natl Acad Sci USA. 1991;88(9):3767−3771. doi: 10.1073/pnas.88.9.3767
  23. Boyarskii KYu, Gaidukov SN, Mashkova EA. Rol antimyullerova gormona v norme i pri razlichnih ginekologicheskih zabolevaniyah. Journal of Obstetrics and Women’s Diseases. 2009;LVIII(3):75−85. (In Russ.)
  24. Lindenman E, Shepard MK, Pescovits OH. Müllerian agenesis: an update. Obstet Gynecol. 1997;90(2):307–312. doi: 10.1016/S0029-7844(97)00256-1
  25. Wang J, Dicken C, Lustbader JW, Tortoriello DV. Evidence for a Müllerian-inhibiting substance autocrine/paracrine system in adult human endometrium. Fertil Steril. 2009;91(4):1195−203. doi: 10.1016/j.fertnstert.2008.01.028
  26. Fu YX, Yang HM, OuYang XE, et al. Assessment of Anti-Mullerian hormone and Anti-Mullerian hormone type II receptor variants in women with repeated implantation failures. Reprod Sci. 2021;28(2):406−415. doi: 10.1007/s43032-020-00303-6
  27. Adamjan LV, Kurilo LF, Glybina TM, Makijan ZN. Anomalii razvitija zhenskih polovyh organov: novyj vzgljad na morfogenez. Problemy reprodukcii. 2009;15(4):10−19. (In Russ.)
  28. Chan YY, Jayaprakasan K, Tan A, et al. Reproductive outcomes in women with congenital uterine anomalies: a systematic review. Ultrasound Obstet Gynecol. 2011;38(1):371–382. doi: 10.1002/uog.10056
  29. Kazantseva EV, Tral TG, Tolibova GK. Clinical and anamnestic data and morphofunctional characteristics of the endometrium in women with uterine developmental anomalies. Journal of obstetrics and women’s diseases. 2021;70(2):5−12. (In Russ.). doi: 10.17816/JOWD54605

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Figure. Expression of AMHR2 in the endometrium of the proliferation phase: (a) the secretion phase; (b) immunohistochemistry, ×400

Download (255KB)
Indexing metadata

Copyright (c) 2021 Eсо-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 66759 от 08.08.2016 г. 
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия Эл № 77 - 6389 от 15.07.2002 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies