Evaluation of aromatase expression in endometrioid heterotopias and endometria in patients with external genital endometriosis

Cover Page


Cite item

Full Text

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

Abstract

BACKGROUND: External genital endometriosis is a multifactorial estrogen-dependent disease. Local estrogen production due to aromatase activity can play an important role in its pathogenesis, so aromatase inhibitors are considered promising drugs for the treatment of the disease. However, the data on their effectiveness are contradictory.

AIM: The aim of this study was to evaluate the expression level of the aromatase-encoding CYP19A1 gene in the eutopic endometrium and endometrioid heterotopies of patients with endometriosis and in the eutopic endometrium of women from the comparison group.

MATERIALS AND METHODS: This study included 79 women. The main group consisted of 55 patients with endometriosis, and 24 patients without endometriosis formed a comparison group. All of the patients underwent an endometrial biopsy during surgery, with excision of endometriotic lesions performed in patients with endometriosis. CYP19A1 gene expression was studied using reverse transcription real-time polymerase chain reaction.

RESULTS: The data obtained confirm a high level of aromatase expression in endometriosis foci. On average, aromatase expression is increased in the eutopic endometrium of patients with endometriosis when compared to the endometrium of women in the comparison group. However, in a significant number of patients with endometriosis, aromatase is expressed in the endometrium at a low level. We did not find an association of increased aromatase expression with any clinical and anamnestic features of the studied group of women, in particular, with infertility, pain syndrome, prevalence of endometriosis, or relapses of the disease.

CONCLUSIONS: Our findings highlight the heterogeneity of endometriosis and may account for the variable effectiveness of hormone-modulating therapy, in particular aromatase inhibitors.

Full Text

Restricted Access

About the authors

Olga V. Malysheva

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

Email: omal99@mail.ru
ORCID iD: 0000-0002-8626-5071
SPIN-code: 1740-2691

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Arsenii S. Molotkov

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

Email: arseny.molotkov@gmail.com
ORCID iD: 0000-0003-3433-3092
SPIN-code: 6359-6472

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Natalia Yu. Shved

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

Email: natashved@mail.ru
ORCID iD: 0000-0001-6354-9226
SPIN-code: 8276-1720

Cand. Sci. (Biol.)

Russian Federation, Saint Petersburg

Marina A. Mikhailova

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

Email: mmikh020@gmail.com
ORCID iD: 0009-0001-5828-2245
Russian Federation, Saint Petersburg

Maria I. Yarmolinskaya

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

Author for correspondence.
Email: m.yarmolinskaya@gmail.com
ORCID iD: 0000-0002-6551-4147
SPIN-code: 3686-3605

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

Russian Federation, Saint Petersburg

References

  1. Bulun SE, Yilmaz BD, Sison C, et al. Endometriosis. Endocr Rev. 2019;40(4):1048–1079. doi: 10.1210/er.2018-00242
  2. Shafrir AL, Martel E, Missmer SA, et al. Pelvic floor, abdominal and uterine tenderness in relation to pressure pain sensitivity among women with endometriosis and chronic pelvic pain. Eur J Obstet Gynecol Reprod Biol. 2021;264:247–253. doi: 10.1016/j.ejogrb.2021.07.029
  3. Vsemirnaya organizatsiya zdravookhraneniya [Internet]. Endometrioz. (In Russ.) [cited 2023 Apr 17]. Available from: https://www.who.int/news-room/fact-sheets/detail/endometriosis
  4. Nnoaham KE, Hummelshoj L, Webster P, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril. 2011;96(2):366–373.e8. doi: 10.1016/j.fertnstert.2011.05.090.
  5. Sampson JA. Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol. 1927;3(2):93–110.43.
  6. Yarmolinskaya MI, Aylamazyan EK. Genital’nyy endometrioz. Razlichnye grani problemy. Saint Petersburg: Eco-Vector; 2017. (In Russ.)
  7. Kitawaki J, Kado N, Ishihara H, et al. Endometriosis: the pathophysiology as an estrogen-dependent disease. J Steroid Biochem Mol Biol. 2002;83(1–5):149–55. doi: 10.1016/s0960-0760(02)00260-1
  8. Corbin CJ, Graham-Lorence S, McPhaul M, et al. Isolation of a full-length cDNA insert encoding human aromatase system cytochrome P-450 and its expression in nonsteroidogenic cells. Proc Natl Acad Sci USA. 1988;85(23):8948–8952. doi: 10.1073/pnas.85.23.8948
  9. Simpson ER, Mahendroo MS, Means GD, et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev. 1994;15(3):342–355. doi: 10.1210/edrv-15-3-342
  10. Kitawaki J, Noguchi T, Amatsu T, et al. Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in human endometriotic and adenomyotic tissues but not in normal endometrium. Biol Reprod. 1997;57(3):514–519. doi: 10.1095/biolreprod57.3.514
  11. Noble LS, Simpson ER, Johns A, et al. Aromatase expression in endometriosis. J Clin Endocrinol Metab. 1996;81(1):174–179. doi: 10.1210/jcem.81.1.8550748
  12. Noble LS, Takayama K, Zeitoun KM, et al. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab. 1997;82(2):600–606. doi: 10.1210/jcem.82.2.3783
  13. Mori T, Ito F, Koshiba A, et al. Aromatase as a target for treating endometriosis. J Obstet Gynaecol Res. 2018;44(9):1673–1681. doi: 10.1111/jog.13743
  14. Maia H, Haddad C, Casoy J. Correlation between aromatase expression in the eutopic endometrium of symptomatic patients and the presence of endometriosis. Int J Womens Health. 2012;4:61–65. doi: 10.2147/IJWH.S29154
  15. Hatok J, Zubor P, Galo S, et al. Endometrial aromatase mRNA as a possible screening tool for advanced endometriosis and adenomyosis. Gynecol Endocrinol. 2011;27(5):331–336. doi: 10.3109/09513590.2010.491925
  16. Taylor RN, Hummelshoj L, Stratton P, et al. Pain and endometriosis: Etiology, impact, and therapeutics. Middle East Fertil Soc J. 2012;17(4):221–225. doi: 10.3109/09513590.2010.491925
  17. Pavone ME, Bulun SE. Aromatase inhibitors for the treatment of endometriosis. Fertil Steril. 2012;98(6):1370–1379. doi: 10.1016/j.fertnstert.2012.08.053
  18. Attar E, Bulun SE. Aromatase inhibitors: the next generation of therapeutics for endometriosis? Fertil Steril. 2006;85(5):1307–1318. doi: 10.1016/j.fertnstert.2005.09.064
  19. Yarmolinskaya MI, Abashova EI, Misharina EV, et al. Medikamentoznaya terapiya genital’nogo endometrioza: realii i perspektivy: rukovodstvo dlya vrachey. Moscow: GEOTAR-Media; 2021. (In Russ.)
  20. Patent Russian Federation na izobretenie No. 2541089/10.02.2015. Byul. No. 4. Yarmolinskaya MI, Molotkov AS, Bezhenar’ VF. Sposob kompleksnogo lecheniya naruzhnogo genital’nogo endometrioza. (In Russ.) [cited 2023 Sep 12]. Available from: https://viewer.rusneb.ru/ru/000224_000128_0002541089_20150210_C1_RU?page=1&rotate=0&theme=white
  21. Becker CM, Bokor A, Heikinheimo O, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022(2). doi: 10.1093/hropen/hoac009
  22. Colette S, Lousse JC, Defrère S, et al. Absence of aromatase protein and mRNA expression in endometriosis. Hum Reprod. 2009;24(9):2133–2141. doi: 10.1093/humrep/dep199

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Fig. 1. Relative expression of the CYP19A1 gene in the eutopic endometrium and ectopic endometrium of peritoneal heterotopias in various diseases. PID — chronic pelvic inflammatory diseases without exacerbation; PCOS — polycystic ovary syndrome

Download (63KB)
3. Fig. 2. Relative expression of aromatase in the eutopic endometrium of patients with endometriosis depending on the day of the menstrual cycle (a), prevalence of the disease (b), pain (c), infertility (d)

Download (205KB)

Copyright (c) 2023 Eсо-Vector

License URL: https://eco-vector.com/for_authors.php#07

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