mersin univ saglık bilim derg Mersin Üniversitesi Sağlık Bilimleri Dergisi 1308-0830 Mersin University Health Care Administration Sağlık Kurumları Yönetimi Uterine changes in polycystic ovary syndrome Polikistik over sendromunda uterus değişiklikleri https://orcid.org/0000-0003-3221-4292 Batu Öztürk Ayla MERSİN ÜNİVERSİTESİ, TIP FAKÜLTESİ https://orcid.org/0009-0008-9294-942X Kara İlker MERSİN ÜNİVERSİTESİ, TIP FAKÜLTESİ https://orcid.org/0000-0001-8046-8049 Aktaş Savaş MERSİN ÜNİVERSİTESİ, TIP FAKÜLTESİ 08 17 2023 16 2 314 324 03 22 2023 05 29 2023 Copyright © 2008, Mersin Üniversitesi Sağlık Bilimleri Dergisi 2008 Mersin Üniversitesi Sağlık Bilimleri Dergisi

Polycystic ovary syndrome is a metabolic endocrine disease which affects approximately 20% of women who are at reproductive age. However, the etiopathogenesis of this disease is still unclear. It has been reported that changes in the hypothalamus-pituitary-ovarian axis in the polycystic ovary syndrome patients lead to subfertility, infertility and early pregnancy loss. Although there are many studies in the literature about the connection between the clinical findings in this complex syndrome and the structural, functional and metabolic changes observed in the ovary, the mechanisms of the disease on possible uterine dysfunction is poorly understood. Besides, it has been reported that spontaneous abortion and early pregnancy complications are higher in spontaneous pregnancies and pregnancies with ovulation induction treatments and assisted reproductive techniques in polycystic ovary syndrome compared to the normal population. Therefore, the definition of uterine changes in polycystic ovary syndrome and the development of different treatment approaches for polycystic ovary syndrome will shed light to understand the etiopathogenesis of the disease. Particularly such contributions will help to understand how to improve the quality of life in these patients, increasing the pregnancy rates and healthy newborn rates in women of reproductive age. In this review, we summarized the molecular, functional and structural changes that occur in the uterine tissue in polycystic ovary syndrome. Moreover, it is emphasized that uterine dysfunction is an important matter which should be considered in reducing subfertility, infertility and early pregnancy complications in these patients.

Polikistik over sendromu, reprodüktif çağdaki kadınların yaklaşık %20’sini etkileyen metabolik endokrin bir hastalık olup bu hastalığın etiyopatogenezi henüz tam olarak bilinmemektedir. Bu hastalarda hipotalamus-hipofiz-over aksındaki değişikliklerin subfertilite, infertilite ve erken gebelik kayıplarına yol açtığı raporlanmıştır. Literatürde, bu kompleks sendromda saptanan klinik bulguların overde gözlenen yapısal, fonksiyonel ve metabolik değişikliklerle ilişkisi üzerine çok fazla çalışma bulunmasına rağmen, hastalığın olası uterus disfonksiyonu üzerindeki mekanizmaları henüz net olarak açıklanamamıştır. Bunun yanı sıra, polikistik over sendromunda spontan, ovülasyon indüksiyon tedavileri ve yardımcı üreme teknikleri ile oluşan gebeliklerde spontan abortus ve erken gebelik komplikasyonlarının normal popülasyona göre fazla olduğu da bildirilmektedir. Bu nedenle polikistik over sendromunda meydana gelen uterin değişikliklerin tanımlanması ve buna yönelik farklı tedavi yaklaşımlarının geliştirilmesi, bu hastalarda yaşam kalitesinin iyileştirilmesi, reprodüktif çağdaki kadınlarda gebelik ve sağlıklı yeni doğan oranlarının arttırılması açısından literatüre önemli katkılar sağlayacaktır. Bu derlemede, polikistik over sendromunda uterus dokusunda meydana gelen moleküler, fonksiyonel ve yapısal değişiklikler özetlenmeye çalışılmıştır. Ayrıca bu hastalarda subfertilite, infertilite ve erken gebelik komplikasyonlarının azaltılmasında uterin disfonksiyonun göz önüne alınması gereken, önemli bir konu olduğu vurgulanmaya çalışılmıştır.

 Polikistik over sendromu uterus endometriyum miyometriyum Polycystic ovary syndrome uterus endometrium myometrium March WA, Moore VM, Willson KJ, Phillips DIW, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010;25(2):544–551. doi:10.1093/HUMREP/DEP399 Berger JJ, Bates GW. Optimal management of subfertility in polycystic ovary syndrome. Int J Womens Health. 2014;6(1):613–621. doi:10.2147/IJWH.S48527 Rajashekar L, Krishna D, Patil M. Polycystic ovaries and infertility: our experience. J Hum Reprod Sci. 2008;1(2):65. doi:10.4103/0974-1208.44113 Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med. 2010;8. doi:10.1186/1741-7015-8-41 Apparao KBC, Lovely LP, Gui Y, Lininger RA, Lessey BA. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome. Biol Reprod. 2002;66(2):297–304. doi:10.1095/BIOLREPROD66.2.297 Jakubowicz DJ, Essah PA, Seppälä M, vd. Reduced serum glycodelin and insulin-like growth factor-binding protein-1 in women with polycystic ovary syndrome during first trimester of pregnancy. J Clin Endocrinol Metab. 2004;89(2):833–839. doi:10.1210/JC.2003-030975 Shang K, Jia X, Qiao J, Kang J, Guan Y. Endometrial abnormality in women with polycystic ovary syndrome. Reprod Sci. 2012;19(7):674–683. doi:10.1177/1933719111430993 Pathare ADS, Hinduja I, Mahadik RC. Basic aspects of endometrial receptivity in PCOS patients. Mol Biol Rep. 2022;49(2):1519–1528. doi:10.1007/s11033-021-06976-9 Palomba S, Piltonen TT, Giudice LC. Endometrial function in women with polycystic ovary syndrome: a comprehensive review. Hum Reprod Update. 2021;27(3):584–618. doi:10.1093/humupd/dmaa051 Ferreira SR, Motta AB. Uterine function: From normal to polycystic ovarian syndrome Alterations. Curr Med Chem. 2018;25(15):1792–1804. doi:10.2174/0929867325666171205144119 Hosseinzadeh P, Barsky M, Gibbons WE, Blesson CS. Polycystic ovary syndrome and the forgotten uterus. F&S Rev. 2021;2(1):11. doi:10.1016/J.XFNR.2020.12.001 H. RM, Wojciech P. Histology: A Text and Atlas. 7th baskı. Wolters Kluwer; 2016. doi:10.1016/s0046-8177(76)80066-4 Jiang NX, Li XL. The disorders of endometrial receptivity in PCOS and its mechanisms. Reprod Sci. 2022;29(9):2465–2476. doi:10.1007/s43032-021-00629-9 Hu C, Pang B, Ma Z, Yi H. Immunophenotypic profiles in polycystic ovary syndrome. Mediators Inflamm. 2020;2020. doi:10.1155/2020/5894768 Gisela S B, M Virginia A, Gabriela A A, vd. Androgen receptor and uterine histoarchitecture in a PCOS rat model. Mol Cell Endocrinol. 2020;518:110973. doi:10.1016/J.MCE.2020.110973 Mirabolghasemi G, Kamyab Z. Changes of the uterine tissue in rats with polycystic ovary syndrome induced by estradiol valerate. Int J Fertil Steril. 2017;11(1):47. doi:10.22074/IJFS.2016.4794 Hu M, Zhang Y, Feng J, vd. Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats. J Endocrinol. 2018;237(2):123–137. doi:10.1530/JOE-18-0086 Quezada S, Avellaira C, Johnson MC, Gabler F, Fuentes A, Vega M. Evaluation of steroid receptors, coregulators, and molecules associated with uterine receptivity in secretory endometria from untreated women with polycystic ovary syndrome. Fertil Steril. 2006;85(4):1017–1026. doi:10.1016/j.fertnstert.2005.09.053 Hu M, Li J, Zhang Y, vd. Endometrial progesterone receptor isoforms in women with polycystic ovary syndrome. Am J Transl Res. 2018;10(8):2696. Erişim Şubat 16, 2023. /pmc/articles/PMC6129510/ Maliqueo M, Bacallao K, Quezada S, vd. Sex hormone-binding globulin expression in the endometria of women with polycystic ovary syndrome. Fertil Steril. 2007;87(2):321–328. doi:10.1016/j.fertnstert.2006.06.038 Li X, Cui P, Jiang HY, vd. Reversing the reduced level of endometrial GLUT4 expression in polycystic ovary syndrome: a mechanistic study of metformin action. Am J Transl Res. 2015;7(3):574. Erişim Ekim 9, 2022. /pmc/articles/PMC4448196/ Lopes IMRS, Maganhin CC, Oliveira-Filho RM, vd. Histomorphometric analysis and markers of endometrial receptivity embryonic implantation in women with polycystic ovary syndrome during the treatment with progesterone. Reprod Sci. 2014;21(7):930–938. doi:10.1177/1933719113519169 Margarit L, Taylor A, Roberts MH, vd. MUC1 as a discriminator between endometrium from fertile and infertile patients with PCOS and endometriosis. J Clin Endocrinol Metab. 2010;95(12):5320–5329. doi:10.1210/jc.2010-0603 Tal R, Seifer DB, Arici A. The emerging role of angiogenic factor dysregulation in the pathogenesis of polycystic ovarian syndrome. Semin Reprod Med. 2015;33(3):195–207. doi:10.1055/s-0035-1552582 Zhao J, Li D, Tang H, Tang L. Association of vascular endothelial growth factor polymorphisms with polycystic ovarian syndrome risk: a meta-analysis. Reprod Biol Endocrinol. 2020;18(1). doi:10.1186/S12958-020-00577-0 Bacallao K, Plaza-Parrochia F, Cerda A, vd. Levels of regulatory proteins associated with cell proliferation in endometria from untreated patients having polycystic ovarian syndrome with and without endometrial hyperplasia. Reprod Sci. 2016;23(2):211–218. doi:10.1177/1933719115597762 Matteo M, Serviddio G, Massenzio F, vd. Reduced percentage of natural killer cells associated with impaired cytokine network in the secretory endometrium of infertile women with polycystic ovary syndrome. Fertil Steril. 2010;94(6):2222-2227.e3. doi:10.1016/j.fertnstert.2010.01.049 Piltonen TT, Chen J, Erikson DW, vd. Mesenchymal stem/progenitors and other endometrial cell types from women with polycystic ovary syndrome (PCOS) display inflammatory and oncogenic potential. J Clin Endocrinol Metab. 2013;98(9):3765–3775. doi:10.1210/jc.2013-1923 Koc O, Ozdemirici S, Acet M, Soyturk U, Aydin S. Nuclear factor-κB expression in the endometrium of normal and overweight women with polycystic ovary syndrome. J Obstet Gynaecol (Lahore). 2017;37(7):924–930. doi:10.1080/01443615.2017.1315563 Piltonen TT, Chen JC, Khatun M, vd. Endometrial stromal fibroblasts from women with polycystic ovary syndrome have impaired progesterone-mediated decidualization, aberrant cytokine profiles and promote enhanced immune cell migration in vitro. Hum Reprod. 2015;30(5):1203–1215. doi:10.1093/humrep/dev055 Udesen PB, Sørensen AE, Svendsen R, vd. Circulating miRNAs in women with polycystic ovary syndrome: a longitudinal cohort study. Cells. 2023;12(7):1–16. doi:10.3390/cells12070983 Wang W, Ji J, Li J, vd. Several critical genes and microRNAs associated with the development of polycystic ovary syndrome. Ann Endocrinol (Paris). 2020;81(1):18–27. doi:10.1016/j.ando.2019.10.002 Bai X, Zheng L, Li D, Xu Y. Research progress of endometrial receptivity in patients with polycystic ovary syndrome: a systematic review. Reprod Biol Endocrinol. 2021;19(1):1–18. doi:10.1186/s12958-021-00802-4 Sulaiman MAH, Al-Farsi YM, Al-Khaduri MM, Saleh J, Waly MI. Polycystic ovarian syndrome is linked to increased oxidative stress in omani women. Int J Womens Health. 2018;10:763–771. doi:10.2147/IJWH.S166461 Palacio JR, Iborra A, Ulcova-Gallova Z, Badia R, Martínez P. Clinical and experimental immunology the presence of antibodies to oxidative modified proteins in serum from polycystic ovary syndrome patients. Clin Exp Immunol. 2006;144:217–222. doi:10.1111/j.1365-2249.2006.03061.x Mohammadi M. Oxidative stress and polycystic ovary syndrome: a brief review. Published online 2019. doi:10.4103/ijpvm.IJPVM_576_17 Piltonen TT. Polycystic ovary syndrome: endometrial markers. Best Pract Res Clin Obstet Gynaecol. 2016;37:66–79. doi:10.1016/j.bpobgyn.2016.03.008 Kohan K, Carvajal R, Gabler F, Vantman D, Romero C, Vega M. Role of the transcriptional factors FOXO1 and PPARG on gene expression of SLC2A4 in endometrial tissue from women with polycystic ovary syndrome. Reproduction. 2010;140(1):123–131. doi:10.1530/REP-10-0056 Hu M, Zhang Y, Feng J, vd. Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats. J Endocrinol. 2018;237(2):123–137. doi:10.1530/JOE-18-0086 Lohrasbi P, Karbalay-Doust S, Tabei SMB, vd. The effects of melatonin and metformin on histological characteristics of the ovary and uterus in letrozole-induced polycystic ovarian syndrome mice: a stereological study. Int J Reprod Biomed. 2022;20(11):973. doi:10.18502/IJRM.V20I11.12365 Bracho GS, Altamirano GA, Kass L, Luque EH, Bosquiazzo VL. Hyperandrogenism induces histo-architectural changes in the rat uterus. Reprod Sci. 2019;26(5):657–668. doi:10.1177/1933719118783881/METRICS Aktas S, Un I, Omer Barlas I, Ozturk AB, Ilkay Karagul M. Evaluation of the Rho A/Rho-kinase pathway in the uterus of the rat model of polycystic ovary syndrome. Reprod Biol. 2019;19(1):45–54. doi:10.1016/J.REPBIO.2019.01.005 Leonhardt H, Gull B, Kishimoto K, vd. Uterine morphology and peristalsis in women with polycystic ovary syndrome. http://dx.doi.org/101258/ar2012120384. 2012;53(10):1195–1201. doi:10.1258/AR.2012.120384 Sajadi M, Noroozzadeh M, Bagheripour F, Tehrani FR. Contractions in the isolated uterus of a rat model of polycystic ovary syndrome compared to controls in adulthood. Int J Endocrinol Metab. 2018;16(2):63135. doi:10.5812/ijem.63135 Wang Q qing, Guo X cui, Li L, Gao Z hui, Ji M. Treatment with metformin and sorafenib alleviates endometrial hyperplasia in polycystic ovary syndrome by promoting apoptosis via synergically regulating autophagy. J Cell Physiol. 2019;235(2):1339–1348. doi:10.1002/JCP.29051