Human induced pluripotent stem cells and male infertility: an overview of current progress and perspectives

Abstract

Recently, 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 and in 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 accumulating evidence suggests that there are crucial differences between human and mouse PGC specification. Unlike mouse iPSCs (miPSCs) in naive state, hiPSCs exhibit a primed pluripotency which possess less potential for the germ cell fate. Based on research in mice, male germ cells at different stages have been derived from hiPSCs with different protocols, including spontaneous differentiation, overexpression of germ cell regulators, addition of cytokines, co-culture with gonadal cells in vitro and xeno-transplantation. The aim of this review is to summarize the current advances in derivation of male germ cells from hiPSCs and raise the perspectives of hiPSCs in medical application for male infertility, as well as in basic research for male germ cell development.

Keywords: embryonic stem cells; extracellular vesicles; gene editing; germ cell differentiation; induced pluripotent stem cells; male infertility; primordial germ cells; reproductive medicine.

Figure 1

Derivation and application of patient-specific induced pluripotent stem cells (iPSCs) in male infertility. Different types of somatic cells derived from patients with idiopathic infertility are reprogrammed into iPSCs and then differentiated into male germ cells by multiple methods. If necessary, iPSCs with known genetic defects may be corrected by genome editing technology. These cells can be used for in vitro disease modeling, regeneration research and cell-based therapy. In disease modeling, comparison between patients- and normal derived cells potentially provides novel clues to the underlying mechanisms for idiopathic male infertility, which may further lead to the development of therapeutic strategies. PBMCs, peripheral blood mononuclear cells; SSC, spermatogonial stem cell; PGCLCs, human primordial germ cells-like cells.