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Mechanisms regulating mammalian spermatogenesis and fertility recovery following germ cell depletion

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Abstract

Mammalian spermatogenesis is a highly complex multi-step process sustained by a population of mitotic germ cells with self-renewal potential known as spermatogonial stem cells (SSCs). The maintenance and regulation of SSC function are strictly dependent on a supportive niche that is composed of multiple cell types. A detailed appreciation of the molecular mechanisms underpinning SSC activity and fate is of fundamental importance for spermatogenesis and male fertility. However, different models of SSC identity and spermatogonial hierarchy have been proposed and recent studies indicate that cell populations supporting steady-state germline maintenance and regeneration following damage are distinct. Importantly, dynamic changes in niche properties may underlie the fate plasticity of spermatogonia evident during testis regeneration. While formation of spermatogenic colonies in germ-cell-depleted testis upon transplantation is a standard assay for SSCs, differentiation-primed spermatogonial fractions have transplantation potential and this assay provides readout of regenerative rather than steady-state stem cell capacity. The characterisation of spermatogonial populations with regenerative capacity is essential for the development of clinical applications aimed at restoring fertility in individuals following germline depletion by genotoxic treatments. This review will discuss regulatory mechanisms of SSCs in homeostatic and regenerative testis and the conservation of these mechanisms between rodent models and man.

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Acknowledgements

We would like to thank Julien Legrand for helpful discussions and comments. An ARC Future Fellowship (FT140101029) supported R. M. H. and H. M. L. is supported by an Australian Government Research Training Program (RTP) Scholarship. The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and Australian Government.

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  1. Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, 3800, Australia

    Hue M. La & Robin M. Hobbs

  2. Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, 3800, Australia

    Hue M. La & Robin M. Hobbs

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La, H.M., Hobbs, R.M. Mechanisms regulating mammalian spermatogenesis and fertility recovery following germ cell depletion. Cell. Mol. Life Sci. 76, 4071–4102 (2019). https://doi.org/10.1007/s00018-019-03201-6

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