Abstract

Spermatogonial stem cells (SSCs) are the basis of spermatogenesis, which is dependent on the ability to self-renew and differentiation. Controlling self-renewal and differentiation of SSCs could apply to treatment of disease such as male infertility. Recently, in the field of stem cell research, it was demonstrated that effective increase in stem cell activity can be achieved by using growth factors derived from plant extracts. In this study, our aim is to investigate components from natural plant to improve the self-renewal of SSCs. To find the components, germ cells were cultured with comprehensive natural plant extracts, and then the more pure fraction, and finally single compound at different concentrations. As a result, we found 5H-purin-6-amine at 1 µg/mL, originated from Sedum sarmentosum, was a very effective compound induced SSCs proliferation. Our data showed that germ cells cultured with 5H-purin-6-amine could maintain their stable characteristics. Furthermore, transplantation results demonstrated that 5H-purin-6-amine at 1 µg/mL increased the activity of SSCs, indicating the compound could increase true SSC concentration within germ cells to 1.96-fold. These findings would be contributed to improve further reproductive research and treat male infertility by using natural plant extracts.

Highlights

  • Approaches to using small molecules have become increasingly powerful tools for stem cell biology and reprogramming[5] because these types of molecules are involved in various mechanisms, such as signaling, www.nature.com/scientificreports/

  • Because glial cell line-derived neurotrophic factors (GDNF) is well known as a critical factor for self-renewal of germ cells enriched for SSCs in a serum-free condition, it was added to all treatments and control groups

  • S. sarmentosum extract was selected for fractionation for further experiments because it exerted the greatest effect on germ cell proliferation including SSCs

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Summary

Introduction

Approaches to using small molecules have become increasingly powerful tools for stem cell biology and reprogramming[5] because these types of molecules are involved in various mechanisms, such as signaling, www.nature.com/scientificreports/. Plant extracts are good experimental resources because plants are exposed to severe environmental changes like cold and dry seasons, and synthesize useful molecules to resist these extreme changes[7,8,9,10] Such plant extracts have been proven to have positive effects on human health[11,12,13,14]. It has been reported that plant extracts enhanced the recovery rate and function of hematopoietic stem cells and injured kidney cells, respectively[22, 23]. Based on these previous results, we hypothesized that the 11 natural plants, especially related to improvement of sperm motility[24, 25], would promote SSC self-renewal and proliferation. S. sarmentosum extract might be involved in the regulatory mechanism of various cells

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