Top

Published in:

01-10-2017 | Review

Pathobiology of myomatosis uteri: the underlying knowledge to support our clinical practice

Authors: Luz Angela Torres-de la Roche, Sven Becker, Cristina Cezar, Anja Hermann, Angelika Larbig, Lasse Leicher, Attilio Di Spiezio Sardo, Vasilis Tanos, Markus Wallwiener, Hugo Verhoeven, Rudy Leon De Wilde

Published in: Archives of Gynecology and Obstetrics | Issue 4/2017

Abstract

Introduction

Uterine myomatosis, a benign condition, is the most common indication for hysterectomies worldwide, affecting the reproductive goals and quality of health of women. However, gynecologists have been provided with interesting insights on its pathobiology, which are the basis for uterine-preserving therapies. The aim of this paper is to discuss the latest evidence on these mechanisms and its importance in the clinical practice.

Method

A comprehensive literature search was made in Pubmed, Medline, the Cochrane Library, Orbis plus and Google Scholar for articles related to the epidemiological, biological, and genetic bases.

Results

There is extensive evidence that genetic, epigenetic, hormonal, environmental, proinflamatory, angiogenetic, and growing factors are involved in the biology of myomatosis. Such factors are capable of activating and promoting inhibitory signaling pathways leading to initiation, development, and regression of myomata through changes in myometrial cells and myomata fibers, such as cellular proliferation, differentiation, apoptosis, angiogenesis, and changes in the surrounding environment.

Conclusion

A good understanding of the pathobiologic mechanisms of myomatosis gives reasons to physicians to elect conservative or combined therapies, and allow affected women to receive an individualized management, according to age, reproduction desire, and clinical condition.

Ciavattini A, Di Giuseppe J, Stortoni P, Montik N, Giannubilo SR, Litta P et al (2013) Uterine fibroids: pathogenesis and interactions with endometrium and endomyometrial junction. Obstet Gynecol Int. doi:10.1155/2013/173184 PubMedPubMedCentral

Commandeur AE, Aaron KS, Teixeira JM (2015) Epidemiological and genetic clues for molecular mechanisms involved in uterine leiomyoma development and growth. Hum Reprod Update 21(5):593–615. doi:10.1093/humupd/dmv030 CrossRefPubMedPubMedCentral

Stewart EA (2015) Uterine fibroids. N Engl J Med 372:1646–1655. doi:10.1056/NEJMcp1411029 CrossRefPubMed

Canevari RA, Pontes A, Rosa FE, Rainho CA, Rogatto SR (2005) Independent clonal origin of multiple uterine leiomyomas that was determined by X chromosome inactivation and microsatellite analysis. Am J Obstet Gynecol 193:1395–1403. doi:10.1016/j.ajog.2005.02.097 CrossRefPubMed

Catherino WH, Eltoukhi HM, Al-Hendy A (2013) Racial and ethnic differences in the pathogenesis and clinical manifestations of uterine leiomyoma. Semin Reprod Med 31(5):370–379. doi:10.1055/s-0033-1348896 CrossRefPubMedPubMedCentral

Mehine M, Mäkinen N, Heinonen HR, Aaltonen LA, Vahteristo P (2014) Genomics of uterine leiomyomas: insights from high-throughput sequencing. Fertil Steril 102:621–629. doi:10.1016/j.fertnstert.2014.06.050 CrossRefPubMed

Ura B, Scrimin F, Arrigoni G, Franchin C, Monasta L, Ricci G (2016) Proteomic approach for the identification of up-regulated proteins involved in the metabolic process of the leiomyoma. Int J Mol Sci 17:540–555. doi:10.3390/ijms17040540 CrossRefPubMedPubMedCentral

Kim JJ, Sefton EC (2012) The role of progesterone signaling in the pathogenesis of uterine leiomyoma. Mol Cell Endocrinol 358(2):223–231. doi:10.1016/j.mce.2011.05.044 CrossRefPubMed

Peddada SD, Laughlin SK, Miner K, Guyon J-P, Haneke K, Vahdat HL, Semelka RC, Kowalik A, Armao D, Davis B et al (2008) Growth of uterine leiomyomata among premenopausal black and white women. Proc Natl Acad Sci USA 105:19887–19892. doi:10.1073/pnas.0808188105 CrossRefPubMedPubMedCentral

10.

Freed M, Spies J (2010) Uterine artery embolization for fibroids: a review of current outcomes. Semin Reprod Med 28:235–241. doi:10.1055/s-0030-1251480 CrossRefPubMed

11.

Helal A, Mashaly A, Amer T (2010) Uterine artery occlusion for treatment of symptomatic uterine myomas. JSLS 4:386–390. doi:10.4293/108680810X12924466007403 CrossRef

12.

Wang H, Zhao J, Li X, Li P, Lu C, Tian S, Wang Z (2016) The indication and curative effect of hysteroscopic and laparoscopic myomectomy for type II submucous myomas. BMC Surg. doi:10.1186/s12893-016-0124-7

13.

Mehine M, Kaasinen E, Mäkinen N, Katainen R, Kämpjärvi K, Pitkänen E et al (2013) Characterization of uterine leiomyomas by whole-genome sequencing. N Engl J Med 369(1):43–53. doi:10.1056/NEJMoa1302736 CrossRefPubMed

14.

Islam S, Protic O, Stortoni P, Grechi G, Lamanna P, Petraglia F et al (2013) Complex networks of multiple factors in the pathogenesis of uterine leiomyoma. Fertil Steril 100:178–193. doi:10.1016/j.fertnstert.2013.03.00 CrossRefPubMed

15.

Ono M, Bulun SE, Maruyama T (2014) Tissue-specific stem cells in the myometrium and tumor-initiating cells in leiomyoma. Biol Reprod 91(6):1–7. doi:10.1095/biolreprod.114.123794 CrossRef

16.

Mehine M, Kaasinen E, Heinonen HR, Mäkinen N, Kämpjärvi K, Sarvilinna N et al (2016) Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers. PNAS 113(5):1315–1320. doi:10.1073/pnas.1518752113 CrossRefPubMedPubMedCentral

17.

Walker CL (2011) Epigenomic reprogramming of the developing reproductive tract and disease susceptibility in adulthood. Birth Defects Res A Clin Mol Teratol 91:666–671. doi:10.1002/bdra.20827 CrossRefPubMedPubMedCentral

18.

Moravek MB, Yin P, Ono M, Coon JS, Dyson NT, Navarro A et al (2015) Ovarian steroids, stem cells and uterine leiomyoma: therapeutic implications. Hum Reprod Update 21(1):1–12. doi:10.1093/humupd/dmu048 CrossRefPubMed

19.

Donnez J, Tatarchuk TF, Bouchard P, Puscasiu L, Zakharenko NF et al (2012) Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med 366(5):409–420. doi:10.1056/NEJMoa1103182 CrossRefPubMed

20.

Borahay MA, Al-Hendy A, Kilic GS, Boehning D (2015) Signaling pathways in leiomyoma: understanding pathobiology and implications for therapy. Mol Med 21:242–256. doi:10.2119/molmed.2014.00053 CrossRefPubMedPubMedCentral

21.

Deng L, Wu T, Chen XY, Xie L, Yang J (2012) Selective estrogen receptor modulators (SERMs) for uterine leiomyomas. Cochrane Database Syst Rev 10:CD005287PubMed

22.

De Vivo A, Mmancuso A, Giacobbe A, Maggio Savasta L, de Dominici R, Dugo N et al (2011) Uterine myomas during pregnancy: a longitudinal sonographic study. Ultrasound Obstet Gynecol 37:361–365. doi:10.1002/uog.8826 CrossRefPubMed

23.

Laughlin SK, Herring AH, Savitz DA, Olshan AF, Fielding JR, Hartmann KE, Baird DD (2010) Pregnancy-related fibroid reduction. Fertil Steril 94:2421–2423. doi:10.1016/j.fertnstert.2010.03.035 CrossRefPubMedPubMedCentral

24.

Cesen-Cummings K, Houston KD, Copland JA, Moorman VJ, Walker CL, Davis BJ (2003) Uterine leiomyomas express myometrial contractile-associated proteins involved in pregnancy-related hormone signaling. J Soc Gynecol Investig 10:11–20CrossRefPubMed

25.

Simon C (2014) Are we advancing in our scientific understanding and therapeutic improvement of uterine fibroids or not? Fertil Steril 102(3):611–612. doi:10.1016/j.fertnstert.2014.07.1210 CrossRefPubMed

26.

Ciarmela P, Bloise E, Gray PC, Carrarelli P, Islam S, De Pascalis F et al (2011) Activin-A and myostatin response and steroid regulation in human myometrium: disruption of their signalling in uterine fibroid. J Clin Endocrinol Metab 96(3):755–765. doi:10.1210/jc.2010-0501 CrossRefPubMed

27.

Ciarmela P, Islam MS, Reis FM, Gray PC, Bloise E, Petraglia F, Vale W, Castellucci M (2011) Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. Hum Reprod Update 17:772–790. doi:10.1093/humupd/dmr031 CrossRefPubMedPubMedCentral

28.

Tal R, Segars JH (2014) The role of angiogenic factors in fibroid pathogenesis: potential implications for future therapy. Hum Reprod Update 20(2):194–216. doi:10.1093/humupd/dmt042 CrossRefPubMed

29.

Katz TA, Yang Q, Treviño LS, Walker CL, Al-Hendy A (2016) Endocrine-disrupting chemicals and uterine fibroids. Fertil Steril 106(4):967–997. doi:10.1016/j.fertnstert.2016.08.023 CrossRefPubMed

30.

Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS et al (2015) EDC-2: the endocrine society’s second scientific statement on endocrine-disrupting chemicals. Endocr Rev 36:E1–E150. doi:10.1210/er.2015-1010 CrossRefPubMedPubMedCentral

31.

Malik M, Segars J, Catherino WH (2012) Integrin β1 regulates leiomyoma cytoskeletal integrity and growth. Matrix Biol 31(7–8):389–397. doi:10.1016/j.matbio.2012.09.005 CrossRefPubMedPubMedCentral

32.

Sabry M, Halder SK, Allah RE, Rajaratnam V, Al-Hendy A (2013) Serum vitamin D3 level inversely correlates with uterine fibroid volume in different ethnic groups: a crosssectional observational study. Int J Womens Health 5:93–100. doi:10.2147/IJWH.S38800 PubMedPubMedCentral

33.

Miura S, Newaz Khan K, Kitajima M, Hiraki K, Moriyama S, Masuzaki H et al (2006) Differential infiltration of macrophages and prostaglandin production by different uterine leiomyomas. Hum Reprod. doi:10.1093/humrep/del205 PubMed

34.

Chegini N (2010) Proinflammatory and profibrotic mediators: principal effectors of leiomyoma development as a fibrotic disorder. Semin Reprod Med 28(3):180–203. doi:10.1055/s-0030-1251476 CrossRefPubMedPubMedCentral

Title: Pathobiology of myomatosis uteri: the underlying knowledge to support our clinical practice
Authors: Luz Angela Torres-de la Roche
Sven Becker
Cristina Cezar
Anja Hermann
Angelika Larbig
Lasse Leicher
Attilio Di Spiezio Sardo
Vasilis Tanos
Markus Wallwiener
Hugo Verhoeven
Rudy Leon De Wilde
Publication date: 01-10-2017
Publisher: Springer Berlin Heidelberg
Published in: Archives of Gynecology and Obstetrics / Issue 4/2017
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-017-4494-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Pathobiology of myomatosis uteri: the underlying knowledge to support our clinical practice

Abstract

Introduction

Method

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Method

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2017

Comparison of the effect between pioglitazone and metformin in treating patients with PCOS:a meta-analysis

A prospective cohort study on the prediction of fetal distress and neonatal status with arterial and venous Doppler measurements in appropriately grown term fetuses

Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome

Papillomavirus genotyping on formaldehyde fixed paraffin-embedded tissues in vulvar intraepithelial neoplasia

Efficacy and safety of misoprostol, dinoprostone and Cook’s balloon for labour induction in women with foetal growth restriction at term

Changes in incontinence after hysterectomy