scholarly journals Derivation of male germ cells from induced pluripotent stem (iPS) cells: a novel and crucial source for generating male gametes

2012 ◽  
Vol 14 (4) ◽  
pp. 516-517 ◽  
Author(s):  
Zuping He
Reproduction ◽  
2014 ◽  
Vol 147 (6) ◽  
pp. R179-R188 ◽  
Author(s):  
Jingmei Hou ◽  
Shi Yang ◽  
Hao Yang ◽  
Yang Liu ◽  
Yun Liu ◽  
...  

Infertility is a major and largely incurable disease caused by disruption and loss of germ cells. It affects 10–15% of couples, and male factor accounts for half of the cases. To obtain human male germ cells ‘especially functional spermatids’ is essential for treating male infertility. Currently, much progress has been made on generating male germ cells, including spermatogonia, spermatocytes, and spermatids, from various types of stem cells. These germ cells can also be used in investigation of the pathology of male infertility. In this review, we focused on advances on obtaining male differentiated germ cells from different kinds of stem cells, with an emphasis on the embryonic stem (ES) cells, the induced pluripotent stem (iPS) cells, and spermatogonial stem cells (SSCs). We illustrated the generation of male differentiated germ cells from ES cells, iPS cells and SSCs, and we summarized the phenotype for these stem cells, spermatocytes and spermatids. Moreover, we address the differentiation potentials of ES cells, iPS cells and SSCs. We also highlight the advantages, disadvantages and concerns on derivation of the differentiated male germ cells from several types of stem cells. The ability of generating mature and functional male gametes from stem cells could enable us to understand the precise etiology of male infertility and offer an invaluable source of autologous male gametes for treating male infertility of azoospermia patients.


2012 ◽  
Vol 14 (4) ◽  
pp. 574-579 ◽  
Author(s):  
Yong Zhu ◽  
Hong-Liang Hu ◽  
Peng Li ◽  
Shi Yang ◽  
Wei Zhang ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Peng Li ◽  
Hongliang Hu ◽  
Shi Yang ◽  
Ruhui Tian ◽  
Zhenzhen Zhang ◽  
...  

Generation of germ cells from pluripotent stem cellsin vitrocould have great application for treating infertility and provides an excellent model for uncovering molecular mechanisms controlling gametogenesis. In this study, we explored the differentiation potential of mouse induced pluripotent stem (iPS) cells towards male germ cells. Embryoid body formation and retinoic acid/testosterone induction were applied to promote differentiation of mouse iPS cells into male germ cellsin vitro. Quantitative RT-PCR and immunoflourescence were performed to characterize the iPS cell differentiation process, and notably there were different temporal expression profiles of male germ cell-associated genes. The expression of proteins, including MVH, CDH1, and SCP3, was remarkably increased. mRNA expression ofStra8,Odf2,Act, andPrm1was upregulated in iPS cells by retinoic acid or testosterone induction, whereasOct-4transcription was reduced in these cells compared to the controls. Hormones were also measured in the EB medium. DNA content analysis by flow cytometry revealed that iPS cells could differentiate into haploid cells through retinoic acid or testosterone treatment. Collectively, our results suggest that mouse iPS cells possess the potency to differentiate into male germ cellsin vitrothrough embryoid body formation and retinoic acid or testosterone induction.


2019 ◽  
Vol 121 (3) ◽  
pp. 2159-2169
Author(s):  
Javad Amini Mahabadi ◽  
Abolfazl Aazami Tameh ◽  
Sayyed Alireza Talaei ◽  
Mohammad Karimian ◽  
Tahereh Rahiminia ◽  
...  

Reproduction ◽  
2017 ◽  
Vol 153 (2) ◽  
pp. 211-220 ◽  
Author(s):  
Shi Yang ◽  
Qingqing Yuan ◽  
Minghui Niu ◽  
Jingmei Hou ◽  
Zijue Zhu ◽  
...  

Generation of male germ cells from pluripotent cells could provide male gametes for treating male infertility and offer an ideal model for unveiling molecular mechanisms of spermatogenesis. However, the influence and exact molecular mechanisms, especially downstream effectors of BMP4 signaling pathways, in male germ cell differentiation of the induce pluripotent stem (iPS) cells, remain unknown. This study was designed to explore the role and mechanism of BMP4 signaling in the differentiation of mouse iPS cells to male germ cells. Embryoid body (EB) formation and recombinant BMP4 or Noggin were utilized to evaluate the effect of BMP4 on male germ cell generation from mouse iPS cells. Germ cell-specific genes and proteins as well as the downstream effectors of BMP4 signaling pathway were assessed using real-time PCR and Western blots. We found that BMP4 ligand and its multiple receptors, including BMPR1a, BMPR1b and BMPR2, were expressed in mouse iPS cells. Real-time PCR and Western blots revealed that BMP4 could upregulate the levels of genes and proteins for germ cell markers in iPS cells-derived EBs, whereas Noggin decreased their expression in these cells. Moreover, Smad1/5 phosphorylation, Gata4 transcription and the transcripts of Id1 and Id2 were enhanced by BMP4 but decreased when exposed to Noggin. Collectively, these results suggest that BMP4 promotes the generation of male germ cells from iPS cells via Smad1/5 pathway and the activation of Gata4, Id1 and Id2. This study thus offers novel insights into molecular mechanisms underlying male germ cell development.


2018 ◽  
Vol 110 (4) ◽  
pp. e376-e377
Author(s):  
V. Lu ◽  
A. Parrella ◽  
D. Choi ◽  
M. Irani ◽  
C. O'Neill ◽  
...  

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