Myom, Myometriyum ve Endometriyum Dokularının Bone Morfogenetik Proteini -2 SalgılamaKapasitesinin Karşılaştırılması
Abstract
Giriş: Bone morfogenetik protein-2 (BMP-2), transforming growth faktörü β3 (TGF-β3) ailesinin bir üyesi olup, desidualizasyon ve implantasyonda kritik bir rol oynar. Miyomlar, endometrial reseptivite ve embriyo implantasyonunu olumsuz etkileyebilir. Son çalışmalar, endometrial reseptivitenin temelinde yatan moleküler mekanizmaların anlaşılmasının önemini vurgulamıştır. Bu çalışmanın amacı, intramural, subseröz, submuköz miyomların BMP-2 salgı kapasitesini ve endometrial dokuda BMP-2 seviyelerine olan etkilerini belirlemektir.
Materyal ve Metodlar: Semptomatik miyomlar nedeniyle histerektomi veya miyomektomi geçiren 97 kadın, submuköz (SMM, n=26), intramural (IMM, n=34) ve subseröz (SSM, n=37) olmak üzere üç gruba ayrıldı. Miyom, miyometrium ve endometrial doku örnekleri izole edilip homojenize edildi. Miyom, miyometrium ve endometrium doku örneklerinin BMP-2 konsantrasyonları ELISA kitleri kullanılarak değerlendirildi.
Sonuçlar: BMP-2 seviyeleri, SMM, IMM, ve SSM gruplarının miyom örnekleri arasında anlamlı bir farklılık göstermedi (p>0,05). Ancak, bu gruplar içinde, SMM grubunun endometriumunda en düşük BMP-2 seviyelerini saptandı (2417±720 pg/ml, p değeri <0,05). SSM ve IMM gruplarının endometriumundaki BMP-2 seviyeleri, aynı gruplardaki miyom ve miyometrium örneklerinden daha yüksekti. SMM grubu, endometrium, miyometrium ve miyom dokuları arasında BMP-2 seviyelerinde farklılık göstermedi.
Sonuç: Subseröz, submüköz ve intramural miyomlar endometriyum, miyometrium ve miyomdaki BMP-2 ekspresyonu üzerinde farklı etkiler gösterir. Çalışmamızda SSM ve IMM’ların endometriyumun BMP-2 ekspresyonu üzerine etkisi gösterilememiştir. SMM’lar ise endometriumda BMP-2 salınımını değiştirmiştir. Azalmış BMP-2 seviyeleri, bu hasta grubunda daha sık karşımıza çıkan implantasyonun bozulması ve azalmış gebelik oranlarından sorumlu mekanizma olabilir. BMP-2 seviyelerinin artırılmasını sağlayan tedaviler, gelecek çalışmalar için araştırma konusu olabilir.
Keywords
References
- Arici A, Sozen I. (2000). Transforming growth factor-beta 3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation. Fertility and Sterility, 73(5), 1006-1011.
- Bajekal N, Li TC. (2000). Fibroids, infertility and pregnancy wastage. Human Reproduction Update, 6(6), 614-620.
- Casini ML, Rossi F, Agostini R, Unfer V. (2006). Effects of the position of fibroids on fertility. Gynecolological Endocrinology, 22(2), 106-109.
- Doherty LF, Taylor HS. (2015). Leiomyoma-derived transforming growth factor-beta impairs bone morphogenetic protein-2-mediated endometrial receptivity. Fertility and Sterility, 103(3), 845-852.
- Dokuzeylul Gungor N, Onal M, Madenli AA, Agar M. (2023). Surgical removal of FIGO type 0 and 1 fibroids ameliorates the expression of endometrial proinflammatory transcription factors and receptivity modulators. Fertily and Sterility, 119(3), 504-513.
- Don EE, Middelkoop MA, Hehenkamp WJK, Mijatovic V, Griffioen AW, Huirne JAF. (2023). Endometrial angiogenesis of abnormal uterine bleeding and infertility in patients with uterine fibroids-A Systematic Review. International Journal of Molecular Sciences, 24(8).
- Donnez J, Jadoul P. (2002). What are the implications of myomas on fertility? A need for a debate? Human Reproduction, 17(6), 1424-1430.
- Klatsky PC, Tran ND, Caughey AB, Fujimoto VY. (2008). Fibroids and reproductive outcomes: a systematic literature review from conception to delivery. American Journal of Obstetrics And Gynecology, 198(4), 357-366.
- Li Q, Kannan A, Wang W, Demayo FJ, Taylor RN, Bagchi MK et al. (2007). Bone morphogenetic protein 2 functions via a conserved signaling pathway involving Wnt4 to regulate uterine decidualization in the mouse and the human. The Journal of Biological Chemistry, 282(43), 31725-31732.
- Metwally M, Farquhar CM, Li TC. (2011). Is another meta-analysis on the effects of intramural fibroids on reproductive outcomes needed? Reproductive Biomedicine Online, 23(1), 2-14.
- Munro MG. (2019). Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity. Fertility and Sterility, 111(4), 629-640.
- Pritts EA, Parker WH, Olive DL. (2009). Fibroids and infertility: an updated systematic review of the evidence. Fertility and Sterility, 91(4), 1215-1223.
- Rackow BW, Taylor HS. (2010). Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity. Fertility and Sterility, 93(6), 2027-2034.
- Rogers R, Norian J, Malik M, Christman G, Abu-Asab M, Chen F et al. (2008). Mechanical homeostasis is altered in uterine leiomyoma. American Journal of Obstetrics and Gynecology, 198(4), 474 e471-411.
- Sinclair DC, Mastroyannis A, Taylor HS. (2011). Leiomyoma simultaneously impair endometrial BMP-2-mediated decidualization and anticoagulant expression through secretion of TGF-beta3. The Journal of Clinical Endocrinology and Metabolism, 96(2), 412-421.
- Sunkara SK, Khairy M, El-Toukhy T, Khalaf Y, Coomarasamy A. (2010). The effect of intramural fibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and meta-analysis. Human Reproduction, 25(2), 418-429.
- Unlu C, Celik O, Celik N, Otlu B. (2016). Expression of Endometrial Receptivity Genes Increase After Myomectomy of Intramural Leiomyomas not Distorting the Endometrial Cavity. Reproductive Scicences, 23(1), 31-41. Zhao HJ, Klausen C, Li Y, Zhu H, Wang YL, Leung PC. (2018). Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling. Cell Death and Disease, 9(2), 174.
Abstract
Introduction: Bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor β3 (TGF-β3) family and plays a crucial role in decidualization and implantation. Myomas can adversely affect endometrial receptivity and embryo implantation. Recent studies have highlighted the importance of understanding the molecular mechanisms underlying endometrial receptivity. The aim of this study is to determine BMP-2 secretion capacity of intramural, subserous, submucous myomas and their effects on endometrial tissue BMP-2 levels.
Material- methods: Ninety-seven women who underwent hysterectomy or myomectomy because of symptomatic myomas were divided into three groups as submucous (SMM, n=26), intramural (IMM, n=34), and subserous (SSM, n=37). Myoma, myometrium and endometrial tissue samples were isolated and homogenized. BMP-2 concentrations of myoma, myometrium and endometrium tissue samples were evaluated with ELISA kits.
Results: BMP-2 levels showed no significant difference between myoma samples of SMM, IMM, SSM (p>0,05). Within the groups, endometrium of SMM have the lowest BMP-2 levels (2417±720 pg/ml, p value <0,05). BMP-2 levels in endometrium of SSM and IMM groups were higher than myoma and myometrium of SSM and IMM groups. SMM group did not show any difference in BMP-2 levels in endometrium, myometrium and myoma.
Conclusion: Subserous, submucous and intramural myomas show different effect on BMP-2 expression in endometrium, myometrium and myoma. SSM and IMM have no impact on BMP-2 expression of endometrium. But SMM alter release of BMP-2 in endometrium. Decreased BMP-2 levels may be the responsible mechanism for impared implantation and decreased pregnancy rates in this group of patients. Further investigations may lead to the development of novel therapeutics aimed at restoring BMP-2 levels.
Ethical Statement
Ethical approval was issued by Istanbul Medipol University Ethical Committee with the registration number of 10840098-604.01-E.11889 in 2017.
Supporting Institution
none
Thanks
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References
- Arici A, Sozen I. (2000). Transforming growth factor-beta 3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation. Fertility and Sterility, 73(5), 1006-1011.
- Bajekal N, Li TC. (2000). Fibroids, infertility and pregnancy wastage. Human Reproduction Update, 6(6), 614-620.
- Casini ML, Rossi F, Agostini R, Unfer V. (2006). Effects of the position of fibroids on fertility. Gynecolological Endocrinology, 22(2), 106-109.
- Doherty LF, Taylor HS. (2015). Leiomyoma-derived transforming growth factor-beta impairs bone morphogenetic protein-2-mediated endometrial receptivity. Fertility and Sterility, 103(3), 845-852.
- Dokuzeylul Gungor N, Onal M, Madenli AA, Agar M. (2023). Surgical removal of FIGO type 0 and 1 fibroids ameliorates the expression of endometrial proinflammatory transcription factors and receptivity modulators. Fertily and Sterility, 119(3), 504-513.
- Don EE, Middelkoop MA, Hehenkamp WJK, Mijatovic V, Griffioen AW, Huirne JAF. (2023). Endometrial angiogenesis of abnormal uterine bleeding and infertility in patients with uterine fibroids-A Systematic Review. International Journal of Molecular Sciences, 24(8).
- Donnez J, Jadoul P. (2002). What are the implications of myomas on fertility? A need for a debate? Human Reproduction, 17(6), 1424-1430.
- Klatsky PC, Tran ND, Caughey AB, Fujimoto VY. (2008). Fibroids and reproductive outcomes: a systematic literature review from conception to delivery. American Journal of Obstetrics And Gynecology, 198(4), 357-366.
- Li Q, Kannan A, Wang W, Demayo FJ, Taylor RN, Bagchi MK et al. (2007). Bone morphogenetic protein 2 functions via a conserved signaling pathway involving Wnt4 to regulate uterine decidualization in the mouse and the human. The Journal of Biological Chemistry, 282(43), 31725-31732.
- Metwally M, Farquhar CM, Li TC. (2011). Is another meta-analysis on the effects of intramural fibroids on reproductive outcomes needed? Reproductive Biomedicine Online, 23(1), 2-14.
- Munro MG. (2019). Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity. Fertility and Sterility, 111(4), 629-640.
- Pritts EA, Parker WH, Olive DL. (2009). Fibroids and infertility: an updated systematic review of the evidence. Fertility and Sterility, 91(4), 1215-1223.
- Rackow BW, Taylor HS. (2010). Submucosal uterine leiomyomas have a global effect on molecular determinants of endometrial receptivity. Fertility and Sterility, 93(6), 2027-2034.
- Rogers R, Norian J, Malik M, Christman G, Abu-Asab M, Chen F et al. (2008). Mechanical homeostasis is altered in uterine leiomyoma. American Journal of Obstetrics and Gynecology, 198(4), 474 e471-411.
- Sinclair DC, Mastroyannis A, Taylor HS. (2011). Leiomyoma simultaneously impair endometrial BMP-2-mediated decidualization and anticoagulant expression through secretion of TGF-beta3. The Journal of Clinical Endocrinology and Metabolism, 96(2), 412-421.
- Sunkara SK, Khairy M, El-Toukhy T, Khalaf Y, Coomarasamy A. (2010). The effect of intramural fibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and meta-analysis. Human Reproduction, 25(2), 418-429.
- Unlu C, Celik O, Celik N, Otlu B. (2016). Expression of Endometrial Receptivity Genes Increase After Myomectomy of Intramural Leiomyomas not Distorting the Endometrial Cavity. Reproductive Scicences, 23(1), 31-41. Zhao HJ, Klausen C, Li Y, Zhu H, Wang YL, Leung PC. (2018). Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling. Cell Death and Disease, 9(2), 174.
Details
| Primary Language | English |
|---|---|
| Subjects | Surgery (Other) |
| Journal Section | Original Research Articles |
| Authors | |
| Early Pub Date | April 29, 2025 |
| Publication Date | April 30, 2025 |
| Submission Date | May 5, 2024 |
| Acceptance Date | March 24, 2025 |
| Published in Issue | Year 2025 Volume: 18 Issue: 1 |
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