Effect of bone marrow mesenchymal stem cells transplantation on BMP-15 expression and Graafian follicle count in mice model of endometriosis

In: Majalah Obstetri & Ginekologi · 2019 · vol. 26(3) , pp. 107 · doi:10.20473/mog.v26i32018.107-111 · W2916454352
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Bone marrow mesenchymal stem cell transplantation in an endometriosis mouse model did not alter BMP-15 expression but significantly increased Graafian follicle count compared to controls.

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This laboratory randomized trial in 42 Mus musculus mice evaluated whether bone marrow mesenchymal stem cell (BMSC) transplantation alters ovarian BMP-15 expression and Graafian follicle counts in an endometriosis mouse model, comparing control, endometriosis, and endometriosis + BMSCs groups. Immunohistochemistry showed no statistically significant differences in BMP-15 expression across the groups (ANOVA p=0.273), while Graafian follicular counts differed significantly (Kruskal–Wallis p=0.001), with the endometriosis + BMSCs group having higher follicle numbers than control and endometriosis-only mice. A key limitation explicitly reflected in the results is that BMP-15 expression was not changed despite the follicle-count differences. This paper is centrally about endometriosis — it tests BMSCs in an endometriosis mouse model and measures BMP-15 expression and Graafian follicle counts.

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Abstract

Objectives: To determine the effect of bone marrow mesenchy-mal stem cells (BMSCs) on BMP-15 expression and Graafian follicle count in endometriosis mice.Material and Methods: This study was a laboratory randomized clinical trial on Mus musculus. The object of the study was 42 mice which were divided into 3 groups, the control, endome-triosis, and endometriosis + BMSCs groups. Comparison of BMP-15 expression and Graafian follicle count between groups was evaluated.Results: Immunohistochemical analysis showed that BMP-15 expression in control, endometriosis, and endometriosis + BMSCs groups had p=0.551, p=0.446 and p=0.917 with ANOVA test p=0.273, indicating no statistically significant differences between groups . Graafian follicular count in the three groups had p=0.31, p=0.001, and p=0.006, with the Kruskal-Wallis test p=0.001. Graafian follicles in the endometriosis + BMSCs group were higher than those in control and endometriosis groups.Conclusion:In the endometriosis mouse model with bone mar-row stem cell transplantation the BMP-15 expression in each group did not show a difference, but a significant difference was found in the number of Graafian follicles.
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Objectives

To determine the effect of bone marrow mesenchy-mal stem cells (BMSCs) on BMP-15 expression and Graafian follicle count in endometriosis mice.

Material and methods

This study was a laboratory randomized clinical trial on Mus musculus. The object of the study was 42 mice which were divided into 3 groups, the control, endome-triosis, and endometriosis + BMSCs groups. Comparison of BMP-15 expression and Graafian follicle count between groups was evaluated.

Results

Immunohistochemical analysis showed that BMP-15 expression in control, endometriosis, and endometriosis + BMSCs groups had p=0.551, p=0.446 and p=0.917 with ANOVA test p=0.273, indicating no statistically significant differences between groups . Graafian follicular count in the three groups had p=0.31, p=0.001, and p=0.006, with the Kruskal-Wallis test p=0.001. Graafian follicles in the endometriosis + BMSCs group were higher than those in control and endometriosis groups. Conclusion:In the endometriosis mouse model with bone mar-row stem cell transplantation the BMP-15 expression in each group did not show a difference, but a significant difference was found in the number of Graafian follicles. Xu, B., Guo, N., Shi, W., et al. 2015. Oocyte quality is decreased in women with minimal or mild endometriosis. Persani, L., Rosetti, R., Di Pasquale, E., et al. ,2014. The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders. Epub 2014 Bahtiyar, M.O., Seli, E., Senturk, L.M., et al. 1998. Follicular fluid of women with endometriosis stimulates the proliferation of endometrial stromal cells.13(12);3492-5 Di Pasquale, E., Beck-Peccoz, P., Perani, L.,2004. Hyperagonadotropic ovarian failure associated with inherited mutation of human bone morphogeneticn protein -15 (BMP-15) gene. Hendarto, H., 2007. Profil TNF-, GDF-9 dan Hyalronan pada gangguan folikulogenesis sebagai gambaran penurunan kualitas oosit pasien infertil dengan endometriosis. Sanchez, A.M., Somigliana, E., Vercelini, P., et al. 2016. Endometriosis as a detrimental condition for granulosa cell steroidogenesis and development; From molecular alterations to clinical impact. Journal of Steroid Biochemistry and Molecular Biology, 155:35-46. Lindvall, O. & Kokaia, Z.,2005. Stem cell therapy for human brain disorders. Kidney Int, 68, 1937-9. Watt, F. M.& Driskell, R. R.,2010. The therapeutic potential of stem cells. Philos Trans R Soc Lond B Biol Sci, 365,155-63. Moore, R.K.& Shimasaki S.,2002. Molecular biology and physiological role of the oocyte factor, BMP-15 Sato N, Tsunoda H, Nishida M, et al. Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary. Cancer Res. 2000;60:7052–6. [PubMed] Liu, Kui & Rajareddy, Singareddy & Liu, Lian & Jagarlamudi, Krishna & Boman, Karin & Selstam, Gunnar & Reddy, Pradeep. (2006). Control of mammalian oocyte growth and early follicular development by the oocyte PI3 kinase pathway: New roles for an old timer. Developmental biology. 299. 1-11. 10.1016/j.ydbio.2006.07.038. Otsuka,F., McTavish,K.J., Shimasaki,S.,2011. Integral role of GDF 9 and BMP-15 in ovarian function. Molecule reproduction and development, Vol 78:pp9-21. Knight, P. G. & Glister, C.,2006. TGF-beta superfamily members and ovarian follicle development. Reproduction, 132, 191-206. Rajkovic, A., Pangas, S. A. & Matzuk, M. M.,2006. Follicular Development: Mouse, Sheep, and Human Models. In: PLANT, T. M. & ZELEZNIK, A. J. (eds.) Knobil and Neill's Physiology of Reproduction. 4 ed. London: Elsevier, pp.947-995. McGee, E. A. & Hsueh, A. J.,2000. Initial and cyclic recruitment of ovarian follicles. Endocr Rev, 21, 200-14. Rosen MP, Johnstone E, Addauan-Andersen C, Cedars MI. A lower antral follicle count is associated with infertility. Fertil Steril. 2011 May;95(6):1950-4 Leslie P. Gartner, James L. Hiatt. Color Atlas and Text of Histology. Lippincott Williams & Wilkins, 2012 Lee,H.J., K. Selesmiami, Y.Niikura, T. et al.. 2007. Bone marrow transplantation generates immature oocytes and rescues long term fertility in a preclinical mouse model of chemotherapy indued premature ovarian failure. 25(22): 3198-3204. Jonathan L. Tilly & Joshua Johnson. Recent Arguments Against Germ Cell Renewal in the Adult Human Ovary: Is an Absence of Marker Gene Expression Really Acceptable Evidence of an Absence of Oogenesis? Cell Cycle . Volume 6, 2007 - Issue 8 Hendarto, H., Komarhadi, M., Darmawanti, E. & Widjiati, S.,2013. The Effect of Bone Marrow Transplantation on Oocyte-Granulosa Cell Interaction and Follicular Development of Cisplatin-Induced Ovarian Failure in Rat. J Stem Cell Res Ther, 3, 2. Santoso, B., Sulistiyono, A. (2014). Efektivitas terapi Rat Bone Marrow Stem Cell pada tikus Model Sindroma Ovarium Poli Kistik Terhadap Folikulogenesis, Ekspresi Transforming Growth Faktor B. Penelitian unggulan perguruan tinggi Universitas Airlangga (2014). 1. Copyright of the article is transferred to the journal, by the knowledge of the author, whilst the moral right of the publication belongs to the author. 2. The legal formal aspect of journal publication accessibility refers to Creative Commons Attribution-Non Commercial-Share alike (CC BY-NC-SA), (https://creativecommons.org/licenses/by-nc-sa/4.0/) 3. The articles published in the journal are open access and can be used for non-commercial purposes. Other than the aims mentioned above, the editorial board is not responsible for copyright violation The manuscript authentic and copyright statement submission can be downloaded ON THIS FORM.

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endometriosis

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