scholarly journals Cellular Therapy via Spermatogonial Stem Cells for Treating Impaired Spermatogenesis, Non-Obstructive Azoospermia

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1779
Author(s):  
Nesma E. Abdelaal ◽  
Bereket Molla Tanga ◽  
Mai Abdelgawad ◽  
Sahar Allam ◽  
Mostafa Fathi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Male Infertility ◽  
Cellular Therapy ◽  
Antihypertensive Drugs ◽  
Testicular Biopsy ◽  
Testicular Tissue ◽  
Spermatogonial Stem Cells ◽  
Obstructive Azoospermia ◽  
Promising Alternative ◽  
Major Health Problem

Male infertility is a major health problem affecting about 8–12% of couples worldwide. Spermatogenesis starts in the early fetus and completes after puberty, passing through different stages. Male infertility can result from primary or congenital, acquired, or idiopathic causes. The absence of sperm in semen, or azoospermia, results from non-obstructive causes (pretesticular and testicular), and post-testicular obstructive causes. Several medications such as antihypertensive drugs, antidepressants, chemotherapy, and radiotherapy could lead to impaired spermatogenesis and lead to a non-obstructive azoospermia. Spermatogonial stem cells (SSCs) are the basis for spermatogenesis and fertility in men. SSCs are characterized by their capacity to maintain the self-renewal process and differentiation into spermatozoa throughout the male reproductive life and transmit genetic information to the next generation. SSCs originate from gonocytes in the postnatal testis, which originate from long-lived primordial germ cells during embryonic development. The treatment of infertility in males has a poor prognosis. However, SSCs are viewed as a promising alternative for the regeneration of the impaired or damaged spermatogenesis. SSC transplantation is a promising technique for male infertility treatment and restoration of spermatogenesis in the case of degenerative diseases such as cancer, radiotherapy, and chemotherapy. The process involves isolation of SSCs and cryopreservation from a testicular biopsy before starting cancer treatment, followed by intra-testicular stem cell transplantation. In general, treatment for male infertility, even with SSC transplantation, still has several obstacles. The efficiency of cryopreservation, exclusion of malignant cells contamination in cancer patients, and socio-cultural attitudes remain major challenges to the wider application of SSCs as alternatives. Furthermore, there are limitations in experience and knowledge regarding cryopreservation of SSCs. However, the level of infrastructure or availability of regulatory approval to process and preserve testicular tissue makes them tangible and accurate therapy options for male infertility caused by non-obstructive azoospermia, though in their infancy, at least to date.

Decreased expression of DNA methyltransferases in the testes of patients with non-obstructive azoospermia leads to changes in global DNA methylation levels

2019 ◽  
Vol 31 (8) ◽  
pp. 1386 ◽  
Author(s):  
Fatma Uysal ◽  
Gokhan Akkoyunlu ◽  
Saffet Ozturk
Keyword(s):  
Dna Methylation ◽  
Male Infertility ◽  
De Novo ◽  
Biological Effects ◽  
Testicular Biopsy ◽  
Round Spermatid ◽  
Dna Methyltransferases ◽  
Global Dna Methylation ◽  
Obstructive Azoospermia ◽  
Spermatogenic Cells

DNA methylation plays key roles in epigenetic regulation during mammalian spermatogenesis. DNA methyltransferases (DNMTs) function in de novo and maintenance methylation processes by adding a methyl group to the fifth carbon atom of the cytosine residues within cytosine–phosphate–guanine (CpG) and non-CpG dinucleotide sites. Azoospermia is one of the main causes of male infertility, and is classified as obstructive (OA) or non-obstructive (NOA) azoospermia based on histopathological characteristics. The molecular background of NOA is still largely unknown. DNA methylation performed by DNMTs is implicated in the transcriptional regulation of spermatogenesis-related genes. The aim of the present study was to evaluate the cellular localisation and expression levels of the DNMT1, DNMT3A and DNMT3B proteins, as well as global DNA methylation profiles in testicular biopsy samples obtained from men with various types of NOA, including hypospermatogenesis (hyposperm), round spermatid (RS) arrest, spermatocyte (SC) arrest and Sertoli cell-only (SCO) syndrome. In the testicular biopsy samples, DNMT1 expression and global DNA methylation levels decreased gradually from the hyposperm to SCO groups (P<0.05). DNMT3A expression was significantly decreased in the RS arrest, SC arrest and SCO groups compared with the hyposperm group (P<0.05). DNMT3B expression was significantly lower in the RS arrest and SCO groups than in the hyposperm group (P<0.05). Although both DNMT1 and DNMT3A were localised in the cytoplasm and nucleus of the spermatogenic cells, staining for DNMT3B was more intensive in the nucleus of spermatogenic cells. In conclusion, the findings suggest that significant changes in DNMT expression and global DNA methylation levels in spermatogenic cells may contribute to development of male infertility in the NOA groups. Further studies are needed to determine the molecular biological effects of the altered DNMT expression and DNA methylation levels on development of male infertility.

Failure of a combined clinical- and hormonal-based strategy to detect early spermatogenesis and retrieve spermatogonial stem cells in 47,XXY boys by single testicular biopsy

2012 ◽  
Vol 27 (4) ◽  
pp. 998-1004 ◽  
Author(s):  
I. Gies ◽  
J. De Schepper ◽  
D. Van Saen ◽  
E. Anckaert ◽  
E. Goossens ◽  
...  
Keyword(s):  
Stem Cells ◽  
Testicular Biopsy ◽  
Spermatogonial Stem Cells

scholarly journals Novel Variants in HFM1 Lead to Male Infertility Due to Non-obstructive Azoospermia

2021 ◽  
Author(s):  
Dongdong Tang ◽  
Mingrong Lv ◽  
Yang Gao ◽  
Huiru Cheng ◽  
Kuokuo Li ◽  
...  
Keyword(s):  
Male Infertility ◽  
Y Chromosome ◽  
Testicular Biopsy ◽  
Severe Form ◽  
Testicular Sperm Extraction ◽  
Obstructive Azoospermia ◽  
Sperm Retrieval ◽  
Gene Variation ◽  
Y Chromosome Microdeletions ◽  
Whole Exome

Abstract Background Non-obstructive azoospermia (NOA) is the most severe form of male infertility. More than half of the NOA patients were idiopathic for their etiology, in whom it’s difficult to retrieve sperm despite the application of microsurgical testicular sperm extraction (microTESE). Therefore, we conducted to this study to identify the potential genetic factors responsible for NOA, and investigate the sperm retrieval rate of microTESE for the genetic defected NOA.Methods One NOA patient from a consanguineous family (F1-II-1) and fifty NOA patients from non-consanguineous families were included in the study. Semen analyses, chromosome karyotypes, screening of Y chromosome microdeletions, sex hormone testing, and subsequent testicular biopsy were performed to categorize NOA or obstructive azoospermia. Potentialgenetic variants were identified by whole exome sequencing (WES),and confirmed by Sanger sequencing in F1 II-1. The candidate genes were screened in the other fifty NOA patients. Further experiments including quantitative real time-polymerase chain reaction and western blotting were performed to verify the effects of gene variation on gene expression.Results Normal somatic karyotypes and Y chromosome microdeletions were examined in all patients. Hematoxylin and eosin staining (H&E) of the testicular tissues suggested meiotic arrest, and a novel homozygous HFM1 variant (c.3490C>T: p.Q1164X) was identified in F1 II-1. Furthermore, another homozygous HFM1 variant (c.3470G>A: p.C1157Y) was also verified in F2 II-1 from the fifty NOA patients. Significantly decreased expression levels of HFM1 mRNA and protein were observed in the testicular tissues of these two mutants compared with controls. MicroTESE was performed in these two patients, while no sperm were retrieved. Conclusions Our study identified two novel homozygous variants of HFM1 that are responsible for spermatogenic failure and NOA, even microTESE can not contribute to retrieve sperm in these patients.

scholarly journals Rescue of male infertility through correcting a genetic mutation causing meiotic arrest in spermatogonial stem cells

2021 ◽  
Vol 0 (0) ◽  
pp. 0 ◽  
Author(s):  
Ming-Han Tong ◽  
Jin-Song Li ◽  
Ying-Hua Wang ◽  
Meng Yan ◽  
Xi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Male Infertility ◽  
Spermatogonial Stem Cells ◽  
Genetic Mutation ◽  
Meiotic Arrest

scholarly journals Does prepubertal testicular tissue vitrification influence spermatogonial stem cells (SSCs) viability?

2013 ◽  
Vol 30 (10) ◽  
pp. 1271-1277 ◽  
Author(s):  
Mohammadreza Gholami ◽  
Masoud Hemadi ◽  
Ghasem Saki ◽  
Abolfazl Zendedel ◽  
Ali Khodadadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Testicular Tissue ◽  
Spermatogonial Stem Cells

Identification and characterization of spermatogonial stem cells in human testicular biopsy samples

2009 ◽  
Vol 92 (3) ◽  
pp. S28
Author(s):  
F. Izadyar ◽  
C. Maki ◽  
J. Pacchiarotti ◽  
J. Barritt ◽  
N. Bar-Chama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Testicular Biopsy ◽  
Spermatogonial Stem Cells ◽  
Identification And Characterization

Cryopreservation of mouse testicular tissue: prospect for harvesting spermatogonial stem cells for fertility preservation

2011 ◽  
Vol 95 (7) ◽  
pp. 2399-2403 ◽  
Author(s):  
Sok Siam Gouk ◽  
Yu Feng Jason Loh ◽  
Srinivasan D. Kumar ◽  
Paul F. Watson ◽  
Lilia L. Kuleshova
Keyword(s):  
Stem Cells ◽  
Fertility Preservation ◽  
Testicular Tissue ◽  
Spermatogonial Stem Cells

scholarly journals TCF3 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cells by Targeting PODXL

2021 ◽  
Vol 9 ◽  
Author(s):  
Dai Zhou ◽  
Jingyu Fan ◽  
Zhizhong Liu ◽  
Ruiling Tang ◽  
Xingming Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Activity ◽  
Spermatogonial Stem Cells ◽  
Obstructive Azoospermia ◽  
Helix Loop Helix ◽  
Proliferation And Apoptosis ◽  
Stem Cell Activity ◽  
Normal Spermatogenesis ◽  
Epidermal Growth ◽  
First Time

Spermatogonial stem cells (SSCs) are the initial cells for the spermatogenesis. Although much progress has been made on uncovering a number of modulators for the SSC fate decisions in rodents, the genes mediating human SSCs remain largely unclear. Here we report, for the first time, that TCF3, a member of the basic helix-loop-helix family of transcriptional modulator proteins, can stimulate proliferation and suppress the apoptosis of human SSCs through targeting podocalyxin-like protein (PODXL). TCF3 was expressed primarily in GFRA1-positive spermatogonia, and EGF (epidermal growth factor) elevated TCF3 expression level. Notably, TCF3 enhanced the growth and DNA synthesis of human SSCs, whereas it repressed the apoptosis of human SSCs. RNA sequencing and chromatin immunoprecipitation (ChIP) assays revealed that TCF3 protein regulated the transcription of several genes, including WNT2B, TGFB3, CCN4, MEGF6, and PODXL, while PODXL silencing compromised the stem cell activity of SSCs. Moreover, the level of TCF3 protein was remarkably lower in patients with spermatogenesis failure when compared to individuals with obstructive azoospermia with normal spermatogenesis. Collectively, these results implicate that TCF3 modulates human SSC proliferation and apoptosis through PODXL. This study is of great significance since it would provide a novel molecular mechanism underlying the fate determinations of human SSCs and it could offer new targets for gene therapy of male infertility.

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