The limitations of testicular organoids: are they truly as promising as we believe?

Organoid systems have revolutionised various facets of biological research by offering a three-dimensional (3D), physiologically relevant in vitro model to study complex organ systems. Over recent years, testicular organoids have been publicised as promising platforms for reproductive studies, disease modelling, drug screening, and fertility preservation. However, the full potential of these systems has yet to be realised due to inherent limitations. This paper offers a comprehensive analysis of the current challenges associated with testicular organoid models. Firstly, we address the inability of current organoid systems to fully replicate the intricate spatial organisation and cellular diversity of the in vivo testis. Secondly, we scrutinise the fidelity of germ cell maturation within the organoids, highlighting incomplete spermatogenesis and epigenetic inconsistencies. Thirdly, we consider the technical challenges faced during organoid culture, including nutrient diffusion limits, lack of vasculature, and the need for specialised growth factors. Finally, we discuss the ethical considerations surrounding the use of organoids for human reproduction research. Addressing these limitations in combination with integrating complementary approaches, will be essential if we are to advance our understanding of testicular biology and develop novel strategies for addressing reproductive health issues in males. Testicular organoids (TOs) represent a groundbreaking avenue captivating researchers seeking to understand and restore fertility. While TOs hold remarkable potential, their journey to replicate human spermatogenesis within a laboratory environment remains elusive. This review navigates the landscape of TOs, unveiling their unparalleled potential while dissecting the challenges hindering their success, helping refine these models for transformative clinical applications. Photograph by K. Coward.. This article belongs to the Collection Dedication to Jim Cummins. [ABSTRACT FROM AUTHOR]