In vitro gametogenesis from embryonic stem cells in livestock species: recent advances, opportunities, and challenges to overcome

Pluripotent stem cells (PSC) can be stabilized in vitro from pre-implantation stage embryos (embryonic stem cells, ESC) or by reprogramming adult somatic cells (induced pluripotent stem cells, iPSC). The last decade has seen significant advances in the livestock PSC field, particularly the development of robust methods for long-term culture of PSC from several livestock species. Along with this, considerable progress has been made in understanding the states of cellular pluripotency and what they mean for cell differentiation capacity, and significant efforts are ongoing to dissect the critical signaling pathways required for the maintenance of PSC in different species and distinct states of pluripotency. Among the cell types that can be generated from PSC, the germline holds special importance as they are the genetic link between generations; and devising methods to enable in vitro gametogenesis (IVG) and produce viable gametes could revolutionize animal agriculture, wildlife conservation, and human assisted reproduction alike. Within the last decade, many pivotal studies about IVG were published using rodent models, filling some critical knowledge gaps in the field. Most importantly, the entire female reproductive cycle was reproduced in vitro from mouse ESC. Although complete male gametogenesis in vitro has not yet been reported, significant advances were made showing the capacity of germline stem cell-like cells to generate healthy offspring. In this review, we provide an overview of PSC and advances in the establishment of livestock PSC; we present the breakthroughs made in rodents regarding IVG and the current progress towards livestock IVG, including the importance of a detailed understanding of fetal germline development. Finally, we discuss some key advances that will be critical to enable this technology at scale. Given the potential impact of IVG for animal agriculture, major efforts will likely continue to be employed by research institutions and industry towards the development of methods to achieve efficient generation of gametes in vitro. In vitro gametogenesis (IVG) is the capacity to mimic the reproductive cycle in an in vitro environment. The development of IVG could be a game changer in the human, livestock, and wildlife reproduction fields. Lay Summary In this review, we summarize the current state of livestock embryonic stem cell establishment and the advances in production of sperm and eggs in vitro in rodents and livestock. We also discuss the potential and challenges of developing systems that support in vitro gametogenesis in livestock and the opportunities for this new technology in the reproductive field.

Automated summary

Pluripotent stem cells (PSC) can be obtained from embryos or adult somatic cells, and significant progress has been made in the livestock PSC field, including long-term culture and understanding cellular pluripotency. The germline is particularly important as it plays a crucial role in reproduction, and in vitro gametogenesis (IVG) could have significant implications for agriculture and reproduction. Many studies have been done on IVG in rodents, and this review discusses the current progress and challenges in livestock IVG.