In vivo Gene Transfer into Testis and Sperm: Developments and Future Application

Abstract

Despite significant advances in the treatment of infertility via assisted reproductive technology (ART), the underlying causes of idiopathic male infertility still remain unclear. Accumulating evidence suggests that disorders associated with testicular gene expression may play an important role in male infertility. To be able to fully study the molecular mechanisms underlying spermatogenesis and fertilization, it is necessary to manipulate gene expression in male germ cells. Since there is still no reliable method of recapitulating spermatogenesis culture, the development of alternative transgenic approaches is paramount in the study of gene function in testis and sperm. Established methods of creating transgenic animals rely heavily upon injection of DNA into the pronucleus or the injection of transfected embryonic stem cells into blastocysts to form chimeras. Despite the success of these two approaches for making transgenic and knockout animals, concerns remain over costs and the efficiency of transgene integration. Consequently, efforts are in hand to evaluate alternative methodologies. At present, there is much interest in developing approaches that utilize spermatozoa as vectors for gene transfer. These approaches, including testis mediated gene transfer (TMGT) and sperm mediated gene transfer (SMGT), have great potential as tools for infertility research and in the creation of transgenic animals. The aim of this short review is to briefly describe developments in this field and discuss how these gene transfer methods might be used effectively in future research and clinical arenas.

KEYWORDS:

• gene transfer
• sperm
• testis
• transgenic

Notes

Abbreviations: ART–assisted reproductive technology; DBPs–DNA-binding proteins; SMGT–sperm mediated gene transfer; TMGT–testis mediated gene transfer; IVF–in vitro fertilization; ICSI–intra cytoplasmic sperm injection; GFP–green fluorescent protein; YFP–yellow fluorescent protein; AZF–azoospermia factor (AZF); RBM–RNA-binding-motif; DAZLA–deleted in azoospermia; ES cells–embryonic stem cells; BAC–bacterial artificial chromosome; YAC–yeast artificial chromosome.