Biotechnological approaches to the treatment of aspermatogenic men

Abstract

Aspermatogenesis is a severe impairment of spermatogenesis in which germ cells are completely lacking or present in an immature form, which results in sterility in approximately 25% of patients. Because assisted reproduction techniques require mature germ cells, biotechnology is a valuable tool for rescuing fertility while maintaining biological fatherhood. However, this process involves, for instance, the differentiation of preexisting immature germ cells or the production/derivation of sperm from somatic cells. This review critically addresses four potential techniques: sperm derivation in vitro, germ stem cell transplantation, xenologous systems, and haploidization. Sperm derivation in vitro is already feasible in fish and mammals through organ culture or 3D systems, and it is very useful in conditions of germ cell arrest or in type II Sertoli-cell-only syndrome. Patients afflicted by type I Sertoli-cell-only syndrome could also benefit from gamete derivation from induced pluripotent stem cells of somatic origin, and human haploid-like cells have already been obtained by using this novel methodology. In the absence of alternative strategies to generate sperm in vitro, in germ cells transplantation fertility is restored by placing donor cells in the recipient germ-cell-free seminiferous epithelium, which has proven effective in conditions of spermatogonial arrest. Grafting also provides an approach for ex-vivo generation of mature sperm, particularly using prepubertal testis tissue. Although less feasible, haploidization is an option for creating gametes based on biological cloning technology. In conclusion, the aforementioned promising techniques remain largely experimental and still require extensive research, which should address, among other concerns, ethical and biosafety issues, such as gamete epigenetic status, ploidy, and chromatin integrity.

A Review of New Technologies that may Become Useful for in vitro Production of Boar Sperm

“…; Lo and Domes ; Aponte et al. ). Approaches to fertilize oocytes by ICSI successfully resulted either in offspring or in blastocyst formation.…”

“…Note that SSC transplantations can be made with the use of differentiated stem cells from male PGC but also from differentiated stem cells derived from embryo's (ESC) as well as from induced pluripotent stem cells (iPSC) from somatic tissues (Aponte et al. ; West et al. ; Zeng et al.…”

“…The cultures of self‐renewing and differentiating SSC to produce haploid sperm‐like cells are useful for an alternative for treatment of male infertility (Aponte et al. ; Hendriks et al. ,b).…”

Application of induced pluripotent stem cell and embryonic stem cell technology to the study of male infertility

“…However, ESCs have differentiation capability into male gametes in vitro or in vivo (He, 2012). Japanese scientists recently reported that they utilized mESCs to generate PGCs which, following testis transplantation, could differentiate into spermatozoa in mice (Aponte, Schlatt, & Franca, 2013;Esteves & Agarwal, 2013).…”

The azoospermic male: current knowledge and future perspectives

“…A recent breakthrough report by Japanese scientists at Kyoto University used stem cells from mouse embryos to create primordial germ cells, which were then able to differentiate in spermatozoa after testis transplantation in mice. This topic is the theme of the closing article of this Special Issue, namely the challenges and perspectives of biotechnology and stem cell research to treat the most severe cases of azoospermia and potentially ‘cure' male sterility (17). This article is authored by the group led by Dr. Franca from the Federal University of Minas Gerais, Brazil, in collaboration with Dr. Schlatt from Munster, Germany.…”