Ovarian aromatase activity: evaluation methods and the clinical significance in IVF protocols
- Authors: Yakovlev P.P.1, Krylova J.S.1, Mekina I.D.1, Polyakova V.O.1, Kvetnoy I.M.1, Tarasova M.A.1, Kogan I.Y.1, Gzgzyan A.M.1, Rodichkina V.R.1
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Affiliations:
- Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
- Issue: Vol 67, No 2 (2018)
- Pages: 61-69
- Section: Articles
- URL: https://journal-vniispk.ru/jowd/article/view/8870
- DOI: https://doi.org/10.17816/JOWD67261-69
- ID: 8870
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Abstract
Introduction. Cytochrome P450 aromatase is a key enzyme in the biosynthesis of estrogens from androgens. Some gynecological diseases are accompanied with changes in the activity of ovarian aromatase. Moreover, changes in the acti vity of ovarian aromatase are associated with the response to standard gonadotrophin stimulation in women undergoing in vitro fertilization. A new effective method determining the activity of ovarian aromatase without using ovarian tissue biopsy has been developed.
The purpose of the present study was to compare the detection of ovarian aromatase activity using the ratio of estradiol to AMH on the second day of the menstrual cycle through the immunocytochemical evaluation of aromatase expression in cumulus cells.
Methods. Depending on the activity of the ovarian aromatase, calculated on the second day of the menstrual cycle, 16 patients undergoing IVF protocols were categorized into three groups: eight patients with low activity, four with normal activity, and four with high activity. The patients did not differ in age and BMI. The expression of aromatase in cumulus cells obtained through transvaginal puncture was investigated by the immunocytochemical method.
Results. The fluorescence intensities in the low, normal, and high activity groups were 134 (122–161), 238 (201–251), and 259 (240–299), respectively. Differences between these groups were statistically significant (p = 0.008). There was a pronounced positive correlation between the activity of ovarian aromatase, calculated on day two of the menstrual cycle, and the intensity of aromatase fluorescence in cumulus cells (Spearman, r = 0.75, p = 0.001, n = 16).
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##article.viewOnOriginalSite##About the authors
Pavel P. Yakovlev
Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Author for correspondence.
Email: iakovlevpp@gmail.com
PhD Student
Russian Federation, St. PetersburgJulia S. Krylova
Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: emerald2008@mail.ru
PhD, MD, Scientist. Laboratory of Cell Biology, Department of Pathomorphology
Russian Federation, St. PetersburgIrina D. Mekina
Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: rolerus@mail.ru
Candidate of Biological Sciences. Research Fellow of Department Reproductive Technologies
Russian Federation, St. PetersburgVictoria O. Polyakova
Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: vopol@yandex.ru
Professor, Dr. Sc., Head of Laboratory of Cell Biology, Department of Pathomorphology
Russian Federation, St. PetersburgIgor M. Kvetnoy
Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: igor.kvetnoy@yandex.ru
MD, Professor. Head of the Pathomorphology Department
Russian Federation, St. PetersburgMarina A. Tarasova
Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: tarasova@ott.ru
MD, PhD, Professor
Russian Federation, St. PetersburgIgor Yu. Kogan
Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: ikogan@mail.ru
PhD, AM RAM, Scientific Secretary
Russian Federation, St. PetersburgAlexander M. Gzgzyan
Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: iagmail@ott.ru
MD, Head of Department Reproductive Technologies
Russian Federation, St. PetersburgValeriia R. Rodichkina
Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Email: rolerus@mail.ru
Junior Research Scientist of the Pathomorphology Department
Russian Federation, St. Petersburg, RussiaReferences
- Яковлев П.П. Активность ароматазы Р450 яичников в естественном менструальном цикле и при стимуляции суперовуляции // Журнал акушерства и женских болезней. — 2017. — Т. 66. — № 5. — С. 46–55. [Yakovlev PP. Aromatase P450 activity in the natural menstrual cycle and during controlled ovarian stimulation. Journal of Obstetrics and Women’s Diseases. 2017;66(5):46-55. (In Russ.)]. doi: 10.17816/JOWD66546-55.
- Tesarik J, Mendoza C. Nongenomic effects of 17 beta-estradiol on maturing human oocytes: relationship to oocyte developmental potential. J Clin Endocrinol Metab. 1995;80(4):1438-1443. doi: 10.1210/jcem.80.4.7714121.
- Tesarik J. Direct non-genomic effects of follicular steroids on maturing human oocytes: oestrogen versus androgen antagonism. Hum Reprod Update. 1997;3(2):95-100. doi: 10.1093/humupd/3.2.95.
- Neal MS, Younglai EV, Holloway AC, Foster WG. Aromatase activity in granulosa cells as a predictor of pregnancy potential. Int Congr Ser. 2004;1271:139-142. doi: 10.1016/j.ics.2004.05.022.
- Lamb JD, Zamah AM, Shen S, et al. Follicular fluid steroid hormone levels are associated with fertilization outcome after intracytoplasmic sperm injection. Fertil Steril. 2010;94(3):952-957. doi: 10.1016/j.fertnstert.2009.04.010.
- Mendoza C. Relationship between fertilization results after intracytoplasmic sperm injection, and intrafollicular steroid, pituitary hormone and cytokine concentrations. Hum Reprod. 1999;14(3):628-635. doi: 10.1093/humrep/14.3.628.
- Carpintero NL, Suarez OA, Mangas CC, et al. Follicular steroid hormones as markers of oocyte quality and oocyte development potential. J Hum Reprod Sci. 2014;7(3):187-193. doi: 10.4103/0974-1208.142479.
- Andersen CY. Characteristics of human follicular fluid associated with successful conception after in vitro ferti lization. J Clin Endocrinol Metab. 1993;77(5):1227-1234. doi: 10.1210/jcem.77.5.7521343.
- Mendoza C. Follicular fluid markers of oocyte developmental potential. Hum Reprod. 2002;17(4):1017-1022. doi: 10.1093/humrep/17.4.1017.
- Rabinovici J, Blankstein J, Goldman B, et al. In vitro ferti lization and primary embryonic cleavage are possible in 17 alpha-hydroxylase deficiency despite extremely low intrafollicular 17 beta-estradiol. J Clin Endocrinol Metab. 1989;68(3):693-697. doi: 10.1210/jcem-68-3-693.
- Stratakis CA, Vottero A, Brodie A, et al. The aromatase excess syndrome is associated with feminization of both sexes and autosomal dominant transmission of aberrant P450 aromatase gene transcription. J Clin Endocrinol Metab. 1998;83(4):1348-1357. doi: 10.1210/jcem.83.4.4697.
- Baghaei F, Rosmond R, Westberg L, et al. The CYP19 gene and associations with androgens and abdominal obesity in premenopausal women. Obes Res. 2003;11(4):578-585. doi: 10.1038/oby.2003.81.
- Haiman CA, Hankinson SE, Spiegelman D, et al. A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk. Int J Cancer. 2000;87(2):204-210. doi: 10.1002/1097-0215(20000715)87:2<204::aid-ijc8>3.0.co;2-3.
- Lazaros LA, Hatzi EG, Xita NV, et al. Aromatase (CYP19) gene variants influence ovarian response to standard gonadotrophin stimulation. J Assist Reprod Genet. 2012;29(2):203-209. doi: 10.1007/s10815-011-9673-y.
- Altmäe S, Haller K, Peters M, et al. Aromatase gene (CYP19A1) variants, female infertility and ovarian stimulation outcome: a preliminary report. Reprod Biomed Online. 2009;18(5):651-657. doi: 10.1016/s1472-6483(10)60009-0.
- Тимофеева Е.М., Мишарина Е.В., Николаенков И.П., и др. Методические подходы к определению овариальной ароматазы при синдроме поликистозных яичников // Журнал акушерства и женских болезней. — 2016. — Т. 65. — № 1. — С. 54–61. [Timofeeva EM, Misharina EV, Nikolaenkov IP, et al. Methodological approaches to the definition of ovarian aromatase in polycystic ovary syndrome. Journal of Obstetrics and Women’s Diseases. 2016;65(1):54-61. (In Russ.)]. doi: 10.17816/JOWD65154-61.
- Патент РФ на изобретение № 2619345/15.05.17. Бюл. № 14. Потин В.В., Тарасова М.А., Ярмолинская М.И. и др. Способ оценки ароматазной активности антральных фолликулов яичников. [Patent RUS № 2619345/15.05.17. Byul. No 14. Potin VV, Tarasova MA, Jarmolinskaja MI, et al. Method for ovaries antral follicles aromatase activity assess ment. (In Russ.)]
- Younglai EV, Holloway AC, Lim GE, Foster WG. Synergistic effects between FSH and 1,1-dichloro-2,2-bis(P-chlorophenyl)ethylene (P,P’-DDE) on human granulosa cell aromatase activity. Hum Reprod. 2004;19(5):1089-1093. doi: 10.1093/humrep/deh252.
- Barcelos ID, Donabella FC, Ribas CP, et al. Down-regulation of the CYP19A1 gene in cumulus cells of infertile women with endometriosis. Reprod Biomed Online. 2015;30(5):532-541. doi: 10.1016/j.rbmo.2015.01.012.
- De Abreu LG, Silveira VS, Scrideli CA, et al. Endometriosis does not alter aromatase gene expression (CYP19A1) in mural lutein-granulosa cells of women undergoing assisted reproduction techniques — a pilot study. J Endometriosis. 2011;3(4):177-182. doi: 10.5301/JE.2012.9070.
- Yang F, Ruan YC, Yang YJ, et al. Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women. Reproduction. 2015;150(4):289-296. doi: 10.1530/REP-15-0044.
- Савина В.А. Овариальная ароматаза р450 при нормогонадотропной недостаточности яичников // Журнал акушерства и женских болезней. — 2012. — Т. 61. — № 1. — С. 84–89. [Savina VA. Ovarian aromatase р450 and normogonadotropic ovarian deficiency. Journal of Obstetrics and Women´s Diseases. 2012;61(1):84-89. (In Russ.)]
- Sternberger LA, Hardy PH, Jr., Cuculis JJ, Meyer HG. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970;18(5):315-333. doi: 10.1177/18.5.315.
- Makabe S, Naguro T, Stallone T. Oocyte-follicle cell interactions during ovarian follicle development, as seen by high resolution scanning and transmission electron microscopy in humans. Microsc Res Tech. 2006;69(6):436-449. doi: 10.1002/jemt.20303.
- Adashi EY. Endocrinology of the ovary. Hum Reprod. 1994;9(5):815-827. doi: 10.1093/oxfordjournals.humrep.a138602.
- Hamel M, Dufort I, Robert C, et al. Identification of differentially expressed markers in human follicular cells associated with competent oocytes. Hum Reprod. 2008;23(5):1118-1127. doi: 10.1093/humrep/den048.
- Xita N, Georgiou I, Lazaros L, et al. The synergistic effect of sex hormone-binding globulin and aromatase genes on polycystic ovary syndrome phenotype. Eur J Endocrinol. 2008;158(6):861-865. doi: 10.1530/EJE-07-0905.
- Hosseini E, Mehraein F, Shahhoseini M, et al. Epigenetic alterations of CYP19A1 gene in Cumulus cells and its rele vance to infertility in endometriosis. J Assist Reprod Genet. 2016;33(8):1105-1113. doi: 10.1007/s10815-016-0727-z.
- Самойлович Я.А., Потин В.В., Тарасова М.А., и др. Дефицит овариальной ароматазы как причина нормогонадотропной ановуляции // Российский вестник акушера-гинеколога. — 2015. — Т. 15. — № 2. — С. 25–30. [Samoilo vich YA, Potin VV, Tarasova MA, et al. Ovarian aromatase deficiency as a cause of normogonadotropic anovulation. Rossiiskii vestnik akushera-ginekologa. 2015;15(2):25-30. (In Russ.)]
- Савина В.А., Кветной И.М., Клещев М.А., и др. Овариальная ароматаза р450 при синдроме поликистозных яичников // Медицинский академический журнал. — 2012. — Т. 12. — № 1. — C. 66–72. [Savina VA, Kvetnoy IM, Kleshhev MA, et al. Ovarian aromatase p450 in polycystic ovary syndrome. Med Akad Z. 2012;12(1):66-72. (In Russ.)]
- Николаенков И.П., Потин В.В., Тарасова М.А., и др. Актив ность овариальной ароматазы у больных с синдромом поликистозных яичников // Журнал акушерства и женских болезней. — 2014. — Т. 63. — № 1. — C. 10–16. [Nikolaenkov IP, Potin VV, Tarasova MA, et al. Ovarian aromatase activity in polycystic ovarian syndrome. Journal of Obstetrics and Women´s Diseases. 2014;63(1):10-16. (In Russ.)] doi: 10.17816/JOWD63110-16
- Lazaros L, Xita N, Hatzi E, et al. CYP19 gene variants affect the assisted reproduction outcome of women with polycystic ovary syndrome. Gynecol Endocrinol. 2013;29(5):478-482. doi: 10.3109/09513590.2013.774359.
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