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 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.

scholarly journals PAMAM-cRGD mediating efficient siRNA delivery to spermatogonial stem cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Tianjiao Li ◽  
Qiwen Chen ◽  
Yi Zheng ◽  
Pengfei Zhang ◽  
Xiaoxu Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Male Infertility ◽  
Transfection Efficiency ◽  
Genetically Modified ◽  
Genetic Disorders ◽  
Sirna Delivery ◽  
Spermatogonial Stem Cells ◽  
Pamam Dendrimers ◽  
Endosomal Escape ◽  
Cell Counting

Abstract Background Spermatogonial stem cells (SSCs) are the cornerstone of sperm production and thus perpetual male fertility. In clinics, transplantation of patient’s own SSCs into testes is a promising technique to restore fertility when male germ cells have been depleted by gonadotoxic therapies. Auto-transplantation of genetically modified SSCs even has the potential to treat male infertility caused by genetic mutations. However, SSCs are refractory to transfection approaches. Poly(amidoamine) (PAMAM) dendrimers have the unique three-dimensional architecture, surface charge, and high density of surface groups that are suitable for ligand attachment, thereby facilitating target delivery. The goal of this study was to elucidate whether PAMAM dendrimers can efficiently deliver short interfering RNAs (siRNAs) to SSCs. Methods and results We introduced cyclic arginine-glycine-aspartic acid (cRGD) peptides to the fifth generation of PAMAM dendrimers (G5) to generate PAMAM-cRGD dendrimers (G5-cRGD). The characterization of G5-cRGD was detected by Fourier transform infrared spectroscope (FTIR), transmission electron microscope (TEM), and the Cell Counting Kit-8 (CCK-8) assay. Confocal microscopy and flow cytometry were used to evaluate the delivery efficiency of siRNA by G5-cRGD to SSCs. The results showed that G5-cRGD encompassing siRNA could self-assemble into spherical structures with nanoscale size and possess high transfection efficiency, excellent endosomal escape ability, and low cytotoxicity, superior to a commercial transfection reagent Lipofectamine® 2000. Moreover, we demonstrated that G5-cRGD efficiently delivered siRNAs and triggered gene silencing. Conclusions This study thus provides a promising nanovector for siRNA delivery in SSCs, facilitating the future clinical application of SSC auto-transplantation with genetically modified cells with a hope to cure male infertility that is caused by genetic disorders.

scholarly journals FOXP3 pathogenic variants cause male infertility through affecting the proliferation and apoptosis of human spermatogonial stem cells

Aging ◽  
2019 ◽  
Vol 11 (24) ◽  
pp. 12581-12599
Author(s):  
Qianqian Qiu ◽  
Xing Yu ◽  
Chencheng Yao ◽  
Yujun Hao ◽  
Liqing Fan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Male Infertility ◽  
Spermatogonial Stem Cells ◽  
Pathogenic Variants ◽  
Proliferation And Apoptosis

scholarly journals In Vitro Spermatogenesis by Three-dimensional Culture of Spermatogonial Stem Cells on Decellularized Testicular Matrix

2019 ◽  
Vol 8 ◽  
pp. 1565 ◽  
Author(s):  
Sepideh Ashouri Movassagh ◽  
Mehdi Banitalebi Dehkordi ◽  
Morteza Koruji ◽  
Gholamreza Pourmand ◽  
Parvaneh Farzaneh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Male Infertility ◽  
Culture Medium ◽  
Three Dimensional ◽  
Cell Interaction ◽  
Spermatogonial Stem Cells ◽  
3D Matrix ◽  
Specific Culture

Background: In the males, Spermatogonial Stem Cells (SSCs) contribute to the production of sex cells and fertility. In vitro SSCs culture can operate as an effective strategy for studies on spermatogenesis and male infertility treatment. Cell culture in a three-dimensional (3D) substrate, relative to a two-dimensional substrate (2D), creates better conditions for cell interaction and is closer to in vivo conditions. In the present study, in order to create a 3D matrix substrate, decellularized testicular matrix (DTM) was used to engender optimal conditions for SSCs culture and differentiation. Materials and Methods: After, testicular cells enzymatic extraction from testes of brain-dead donors, the SSCs were proliferated in a specific culture medium for four weeks, and after confirming the identity of the colonies derived from the growth of these cells, they were cultured on a layer of DTM as well as  in 2D condition with a differentiated culture medium. In the Sixth week since the initiation of the differentiation culture, the expression of pre meiotic (OCT4 & PLZF), meiotic (SCP3 & BOULE) and post meiotic (CREM & Protamine-2) genes were measured in both groups. Results: The results indicated that the expression of pre meiotic, meiotic and post meiotic genes was significantly higher in the cells cultured on DTM (P ≤ 0.001). Conclusion: SSCs culture in DTM with the creation of ECM and similar conditions with in vivo can be regarded as a way of demonstrating spermatogenesis in vitro, which can be adopted as a treatment modality for male infertility. [GMJ.2019;8:e1565]

The influence of Robertsonian translocations on semen parameters

2020 ◽  
pp. 87-88
Author(s):  
М.В. Андреева ◽  
М.И. Штаут ◽  
Т.М. Сорокина ◽  
Л.Ф. Курило ◽  
В.Б. Черных
Keyword(s):  
Male Infertility ◽  
Semen Parameters ◽  
Meiotic Arrest ◽  
Robertsonian Translocations ◽  
Prophase I ◽  
Infertile Men ◽  
Fertility Problems ◽  
Spermatogenesis Impairment

Обследованы 19 мужчин с нарушением фертильности, носителей транслокаций rob(13;14) и rob(13;15). Показано, что нарушение репродуктивной функции обусловлено блоком сперматогенеза в профазе I мейоза, приводящего к азооспермии или олигоастенотератозооспермии и мужскому бесплодию. We examined 19 infertile men, carriers of translocations rob (13;14) and rob (13;15). We assume that fertility problems are resulted from spermatogenesis impairment because of meiotic arrest at prophase I stages, that leads to azoospermia or oligoastenoteratozoospermia and male infertility.

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