1. bookVolume 53 (2019): Issue 2 (April 2019)
Journal Details
License
Format
Journal
eISSN
1336-0329
First Published
30 Mar 2016
Publication timeframe
4 times per year
Languages
English
Open Access

Differentiation of bone marrow derived mesenchymal stem cells into male germ-like cells in co-culture with testicular cells

Published Online: 13 May 2019
Volume & Issue: Volume 53 (2019) - Issue 2 (April 2019)
Page range: 93 - 99
Journal Details
License
Format
Journal
eISSN
1336-0329
First Published
30 Mar 2016
Publication timeframe
4 times per year
Languages
English
Abstract

Objective. Stem cell therapy, specifically, pre-induction of mesenchymal stem cells toward male germ-like cells may be useful in patients with azoospermia. The aim of this study was to evaluate in vitro differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs) into male germ-like cells by indirect co-culture with testicular cells in the presence of bone morphogenetic protein 4 (BMP4).

Methods. Experimental groups included: control (mouse BMSCs), treatment group-1 (BMSCs treated with BMP4), treatment group-2 (indirect co-culture of BMSCs with mouse testicular cells in the presence of BMP4) and treatment group-3 (indirect co-culture of BMSCs with testicular cells). BMSCs-derived male germ-like cells were evaluated by the expression of Dazl, and Stra8 using RT-qPCR.

Results. Stra8 gene expression was significantly increased in the treatment group-2 and Dazl gene was significantly increased in the treatment group-1 compared to other groups. In conclusion, indirect co-culturing of BMSCs with testicular cells and BMP4 leads to the differentiation of BMSCs into male germ-like cells which express specific male germ-like genes. Testicular cells released factors that contributed to the differentiation of BMSCs into male germ progenitor cells.

Conclusion. This study suggests that mesenchymal stem cells may be differentiated into male germ-like cells and therefore, may be a novel treatment option for men with azoospermia.

Keywords

de Rooij DG. Proliferation and differentiation of spermatogonial stem cells. Reproduction 121, 347–354, 2001.10.1530/rep.0.1210347Search in Google Scholar

de Sousa Lopes SM, Roelen BA, Monteiro RM, Emmens R, Lin HY, Li E, Lawson KA, Mummery CL. BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. Genes Dev 18, 1838–1849, 2004.10.1101/gad.294004Search in Google Scholar

Dudley BM, Runyan C, Takeuchi Y, Schaible K, Molyneaux K. BMP signaling regulates PGC numbers and motility in organ culture. Mech Dev 124, 68–77, 2007.10.1016/j.mod.2006.09.005Search in Google Scholar

Fabbri A, Knox G, Buczko E, Dufau ML. β-endorphin production by the fetal Leydig cell: Regulation and implications for paracrine control of Sertoli cell function. Endocrinology 122, 749–755, 1998.10.1210/endo-122-2-749Search in Google Scholar

Foresta C, Moro E, Ferlin A. Y chromosome microdeletions and alterations of spermatogenesis. Endocr Rev 22, 226–239, 2001.1129482510.1210/edrv.22.2.0425Search in Google Scholar

Geens M, Sermon KD, Van de Velde H, Tournaye H. Sertoli cell-conditioned medium induces germ cell differentiation in human embryonic stem cells. J Assist Reprod Genet 28, 471–480, 2011.10.1007/s10815-011-9541-9Search in Google Scholar

Gimble JM, Katz AJ, Bunnell BA. Adipose-derived stem cells for regenerative medicine. Circ Res 100, 1249–1260, 2007.10.1161/01.RES.0000265074.83288.09Open DOISearch in Google Scholar

Hamidabadi HG, Pasbakhsh P, Amidi F, Soleimani M, Forouzandeh M, Sobhani A. Functional concentrations of BMP4 on differentiation of mouse embryonic stem cells to primordial germ cells. Int J Fertil Steril 5, 104–109, 2011.Search in Google Scholar

Hansson V, Weddington SC, McLean WS, Smith AA, Nayfeh SN, French FS, Ritzen EM. Regulation of seminiferous tubular function by FSH and androgen. J Reprod Fertil 44, 363–375, 1975.10.1530/jrf.0.0440363Open DOISearch in Google Scholar

Hussein A. Evaluation of diagnostic testis biopsy and the repetition of testicular sperm extraction surgeries in infertility patients. Fertil Steril 100, 88–93, 2013.10.1016/j.fertnstert.2013.03.02223582438Open DOISearch in Google Scholar

Iammarrone E, Balet R, Lower AM, Gillott C, Grudzinskas JG. Male infertility. Best Pract Res Clin Obstet Gynaecol 17, 211–229, 2003.10.1016/S1521-6934(02)00147-5Open DOISearch in Google Scholar

Lacham-Kaplan O, Chy H, Trounson A. Testicular cell conditioned medium supports differentiation of embryonic stem cells into ovarian structures containing oocytes. Stem Cells 24, 266–273, 2006.10.1634/stemcells.2005-020416109761Open DOISearch in Google Scholar

Latifpour M, Shakiba Y, Amidi F, Mazaheri Z, Sobhani A. Differentiation of human umbilical cord matrix-derived mesenchymal stem cells into germ-like cells. Avicenna J Med Biotechnol 6, 218–227, 2014.Search in Google Scholar

Lee JH, Engel W, Nayernia K. Stem cell protein Piwil2 modulates expression of murine spermatogonial stem cell expressed genes. Mol Reprod Dev 73, 173–179, 2006.10.1002/mrd.2039116261612Search in Google Scholar

Makoolati Z, Movahedin M, Forouzandeh-Moghadam M. In vitro germ cell differentiation from embryonic stem cells of mice: induction control by BMP4 signalling. Biosci Rep 36, pii: e00407, 2016.Search in Google Scholar

Margioris AN, Liotta AS, Vaudry H, Bardin CW, Krieger DT. Characterization of immunoreactive proopiomelanocortin-related peptides in rat testes. Endocrinology 113, 663–671, 1983.10.1210/endo-113-2-6636191965Search in Google Scholar

Miryounesi M, Nayernia K, Dianatpour M, Mansouri F, Modarressi MH. Co-culture of mouse embryonic stem cells with Sertoli cells promote in vitro generation of germ cells. Iran J Basic Med Sci 16, 779–783, 2013.Search in Google Scholar

Pellegrini M, Grimaldi P, Rossi P, Geremia R, Dolci S. Developmental expression of BMP4/ALK3/SMAD5 signaling pathway in the mouse testis: a potential role of BMP4 in spermatogonia differentiation. J Cell Sci 116, 3363–3372, 2003.10.1242/jcs.0065012857787Search in Google Scholar

Saitou M, Barton SC, Surani MA. A molecular programme for the specification of germ cell fate in mice. Nature 418, 293–300, 2002.10.1038/nature0092712124616Search in Google Scholar

Saitou M, Payer B, Lange UC, Erhardt S, Barton SC, Surani MA. Specification of germ cell fate in mice. Philos Trans R Soc Lond B Biol Sci 358, 1363–1370, 2003.10.1098/rstb.2003.1324169323014511483Search in Google Scholar

Shirazi R, Zarnani AH, Soleimani M, Abdolvahabi MA, Nayernia K, Ragerdi Kashani I. BMP4 can generate primordial germ cells from bone-marrow-derived pluripotent stem cells. Cell Biol Int 36, 1185–1193, 2012.10.1042/CBI2011065122988836Open DOISearch in Google Scholar

Silva C, Wood JR, Salvador L, Zhang Z, Kostetskii I, Williams CJ, Strauss JF 3rd. Expression profile of male germ cell-associated genes in mouse embryonic stem cell cultures treated with all-trans retinoic acid and testosterone. Mol Reprod Dev 76, 11–21, 2009.10.1002/mrd.20925266438318425777Open DOISearch in Google Scholar

Singh A, Jahan N, Radhakrishnan G, Banerjee BD. To evaluate the efficacy of combination antioxidant therapy on oxidative stress parameters in seminal plasma in the male infertility. J Clin Diagn Res 10, QC14–QC17, 2016.10.7860/JCDR/2016/15597.8159502019927630911Search in Google Scholar

Skinner MK, Fritz IB. Testicular peritubular cells secrete a protein under androgen control that modulates Sertoli cell functions. Proc Natl Acad Sci U S A 82, 114–118, 1985.10.1073/pnas.82.1.1143969823855533Search in Google Scholar

Skinner MK. Cell-cell interactions in the testis. Endocr Rev 12, 45–77, 1991.10.1210/edrv-12-1-45Search in Google Scholar

Surani MA, Ancelin K, Hajkova P, Lange UC, Payer B, Western P, Saitou M. Mechanism of mouse germ cell specification: a genetic program regulating epigenetic reprogramming. Cold Spring Harb Symp Quant Biol 69, 1–9, 2004.10.1101/sqb.2004.69.1Search in Google Scholar

Vannelli BG, Barni T, Orlando C, Natali A, Serio M, Balboni GC. Insulin-like growth factor-1 (IGF-I) and IGF-I receptor in human testis: an immunohistochemical study. Fertil Steril 49, 666–669, 1988.10.1016/S0015-0282(16)59837-9Search in Google Scholar

Walker WH, Cheng J. FSH and testosterone signaling in Sertoli cells. Reproduction 130, 15–28, 2005.10.1530/rep.1.0035815985628Search in Google Scholar

West FD, Roche-Rios MI, Abraham S, Rao RR, Natrajan MS, Bacanamwo M, Stice SL. KIT ligand and bone morphogenetic protein signaling enhances human embryonic stem cell to germ-like cell differentiation. Hum Reprod 25, 168–178, 2010.1984098710.1093/humrep/dep33819840987Search in Google Scholar

Xie L, Lin L, Tang Q, Li W, Huang T, Huo X, Liu X, Jiang J, He G, Ma L. Sertoli cell-mediated differentiation of male germ cell-like cells from human umbilical cord Wharton’s jelly-derived mesenchymal stem cells in an in vitro co-culture system. Eur J Med Res 20, 9, 2015.10.1186/s40001-014-0080-6438997225644284Search in Google Scholar

Yang Y, Feng Y, Feng X, Liao S, Wang X, Gan H, Wang L, Lin X, Han C. BMP4 cooperates with retinoic acid to induce the expression of differentiation markers in cultured mouse spermatogonia. Stem Cells Int 2016, 9536192, 2016.10.1155/2016/9536192506732227795714Search in Google Scholar

Yu Z, Ji P, Cao J, Zhu S, Li Y, Zheng L, Chen X, Feng L. Dazl promotes germ cell differentiation from embryonic stem cells. J Mol Cell Biol 1, 93–103, 2009.10.1093/jmcb/mjp02619783541Search in Google Scholar

Zhang D, Liu X, Peng J, He D, Lin T, Zhu J, Li X, Zhang Y, Wei G. Potential spermatogenesis recovery with bone marrow mesenchymal stem cells in an azoospermic rat model. Int J Mol Sci 15, 13151–13165, 2014.10.3390/ijms150813151415978525062349Open DOISearch in Google Scholar

Zhou Q, Nie R, Li Y, Friel P, Mitchell D, Hess RA, Small C, Griswold MD. Expression of stimulated by retinoic acid gene 8 (Stra8) in spermatogenic cells induced by retinoic acid: an in vivo study in vitamin A-sufficient postnatal murine testes. Biol Reprod 79, 35–42, 2008.10.1095/biolreprod.107.066795320826418322276Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo