GSE126009 Derivation of primodial germ cell-like cells from induced pluripotent stem cells of patients with idiopathic azoospermia

Contributors : Fang Fang ; Zili Li ; Qian Zhao ; Zhen Ye ; Yiting Cai ; Xiuli Gu ; Kai Zhao ; Chunyan Liu ; Hui Zhou ; Tianqing Meng ; Zhe Xiong ; Shiliang Shen ; Honggang Li ; Wenpei Xiang ; Chengliang XiongSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAt present, the etiology of most non-obstructive azoospermia (NOA) remains unclear, and the patients are diagnosed as idiopathic infertility. In vitro generation of patient-specific induced pluripotent stem cells (iPSCs) is an effective approach for exploring the mechanisms of human disease. Here, we established iPSCs from patients with idiopathic NOA, and differentiated them into human germline cells both in vitro and in vivo. Compared with normal hiPSCs, the idiopathic NOA patient-specific iPSCs show less efficiency of primodial germ cell-like cells (PGCLCs) formation in vitro and poor proliferation potential in vivo. Although the transcriptomes of PGCLCs are different from that of embryonic gonadal PGCs, the expression patterns of key genes involved in human PGC specification are generally similar during PGCLC induction process from all iPSCs lines, including the activation of BLIMP1, TFAP2C, NANOS3, SOX17, and T, and the repression of PRDM14 and SOX2. Moreover, the PGCLCs derived from idiopathic NOA patient-specific iPSCs initiate epigenetic reprogramming with repression of 5mC and presence of 5hmC. These findings provide a unique foundation for future mechanism research of male inf...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

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Conclusion The periconceptional environment and lifestyle factors modify sperm epigenome. This alteration might be maintained in the zygote and throughout development, thereby leading to the inheritance of newly acquired pathologies. The role of sperm miRNA, not only as innovative markers of fertility issues but also as vectors involved in the inheritance of paternal diseases, appears to be crucial. Overweight and obesity seem to alter sperm miRNA profile, thereby leading to transmission of different miRNA profiles in zygote, with consequences on embryo development. In long term, metabolic disorders have been described in...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Contributors : Fuchou Tang ; Yidong ChenSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensSpermatogenesis generates mature male gametes and is critical for the proper transmission of genetic information between generations. However, the developmental landscape and underlying molecular signals during human spermatogenesis remain unknown. Here, we examined human spermatogenesis using transcriptome-wide single-cell RNA sequencing of 2,854 individual testicular cells from donors with normal spermatogenesis (donors with normal fertility or OA) and 174 testicular cells from one donor diagnose...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
, Qiao J Abstract Spermatogenesis generates mature male gametes and is critical for the proper transmission of genetic information between generations. However, the developmental landscapes of human spermatogenesis remain unknown. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis for 2,854 testicular cells from donors with normal spermatogenesis and 174 testicular cells from one nonobstructive azoospermia (NOA) donor. A hierarchical model was established, which was characterized by the sequential and stepwise development of three spermatogonia subtypes, seven spermatocyte subtypes, and four s...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
Non-obstructive azoospermia (NOA), particularly Sertoli cell-only (SCO), is the most severe form of male factor infertility and is classically thought to lack germ cells and spermatogenic stem cells (SSCs). However, evidence from microsurgical testicular sperm extraction (micro-TESE) on men with SCO has revealed the presence of focal areas of full spermatogenesis, suggesting the possible presence of SSCs in some patients with SCO lacking mature sperm. To determine whether gene products from SSCs could be detected in SCO, transcriptome analysis using next-generation sequencing (NGS) was performed using human biopsied testicular samples.
Source: The Journal of Urology - Category: Urology & Nephrology Authors: Tags: Infertility: Basic Research & Pathophysiology Source Type: research
In this study, we developed a feeder- and xeno-free culture protocol that efficiently induced human pluripotent stem cells (iPSCs) into PLZF+/GPR125+/CD90+ spermatogonium-like cells (SLCs). These SLCs were enriched with key genes in germ cell development such as MVH, DAZL, GFRα1, NANOS3, and DMRT1. In addition, a small fraction of SLCs went through meiosis in vitro to develop into haploid cells. We further demonstrated that this chemically defined induction protocol faithfully recapitulated the features of compromised germ cell development of PSCs with NANOS3 deficiency or iPSC lines established from patients wi...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
AbstractRecently, significant progress has been made in ART for the treatment of male infertility. However, current ART has failed to help infertile patients with non-obstructive azoospermia, unless donor sperm is used. In fact, most couples wish to have their own genetically related child. Human induced pluripotent stem cells (hiPSCs) can be generated from patients ’ somatic cells andin vitro derivation of functional germ cells from patient-specific iPSCs may provide new therapeutic strategies for infertile couples. The overall developmental dynamics of human primordial germ cells are similar to that in mice, but ac...
Source: Human Reproduction - Category: Reproduction Medicine Source Type: research
CONCLUSION: The present study clearly confirme that a regeneration after cytotoxic treatment was based on morphological criteria. We demonstrated the increase in stem cell numbers during regeneration and after transplantation. Transplantation of spermatogonial stem cells suspension by the injection of cells via the rete testis of recipient azoospermia model considerably enhances the efficiency of this procedure. PMID: 29250763 [PubMed - as supplied by publisher]
Source: Urology Journal - Category: Urology & Nephrology Authors: Tags: Urol J Source Type: research
This study aimed to (a) identify the exogenous factors that allow in vitro differentiation of mouse SSCs from embryonic stem cells (ESCs); (b) evaluate the effects of Sertoli cells on SSCs enrichment; and (c) to assess the success of transplantation using in vitro differentiated SSCs in mouse busulfan-treated azoospermia model. One-day-old embryoid body (EB) received 5 ng/ml BMP4 for 4 days, 3 µM retinoic acid (RA) in STO co-culture (Co-C) system for 7 days and subsequently co-cultured for 2 days with Sertoli cell in the presence or absence of LIF, bFGF and RA composition and in the presence of these factors in the s...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research
AbstractAlthough the technique of intracytoplasmic sperm injection (ICSI) has been a revolution in the alleviation of male infertility, the use of testicular sperm for ICSI was a formerly unseen breakthrough in the treatment of the azoospermic man with primary testicular failure. At the clinical level, different procedures of testicular sperm retrieval (conventional TESE, micro-TESE, FNA/TESA, MESA, PESA) are being performed, the choice is mainly based on the cause of azoospermia (obstructive versus non-obstructive) and the surgeon ’s skills. At the level of the IVF laboratory, mechanical procedures to harvest the sp...
Source: Basic and Clinical Andrology - Category: Urology & Nephrology Source Type: research
This study aimed to investigate the effect of umbilical cord blood-derived stem cells (" and mesenchymal "UCB-MSCs") and mono-cell layer implanted into the induced azoospermic mice testis. Stem cells were isolated from umbilical cord blood and CD34+ve cells were separated from negative one by Mini MACs column. At 5th week after single injection of busulfan, stained mesenchymal (CD34-ve), hematopoietic stem cells (CD34+ve) and their conjugate (mono-cell layer) were injected locally into testis. At the end of the study, MSCs group showed that mRNA levels of genes related to meiosis (Vasa, SCP3, and PgK2) were ...
Source: Molecular and Cellular Biochemistry - Category: Biochemistry Authors: Tags: Mol Cell Biochem Source Type: research
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