Breakthrough Raises Hopes for Restoring Northern White Rhino

Researchers in Japan have induced the precursors of eggs and sperm using cells from threatened white rhinoceros in a critical breakthrough for efforts to rebuild northern white rhino populations.

Despite decades-long efforts to preserve the species through a breeding program, the northern white rhino, or Ceratotherium simum cottoni, is extinct in the wild. Since only two females remain in captivity and the last male died in 2018, new approaches to breeding and conservation are urgently needed. 

Techniques such as artificial insemination, induction of ovulation, and in vitro culture of blastocysts have all been used to advance other breeding programs, but unfortunately there is a lack of northern white rhino eggs and sperm to create embryos.

Previous studies have shown that, in mice, embryonic stem cells can be differentiated into primordial germ cell-like cells (PGCLCs), which are equivalent to the origins of eggs and sperm. PGCLCs have been generated from pluripotent stem cells in mice, humans, monkeys, and rabbits, but never in wild animals.

“Cells from the skin or blood can be reprogrammed back into an embryonic-like state,” says Masafumi Hayashi, lead author of the study. “These cells are called induced pluripotent stem cells, or IPSCs. As with embryonic stem cells, they can develop into any tissue in the body, including sperm and eggs.”

The researchers established a culture system using pluripotent cells from southern and northern white rhinos and through repeated refinement produced PGCLCs. “This is the first time that PGCLCs have been induced in a wild animal,” says Katsuhiko Hayashi, senior author. “This a significant breakthrough as it paves the way for generating reproductive cells from endangered species that can then be used for breeding.”

Production of mature reproductive cells requires a cell environment that provides the chemical signals needed for sex-dependent differentiation and functional maturity of the gametes. In mice, PGCLCs were fully functional after transfer into the ovary and testis. While some challenges remain, in theory, it may be possible to produce mature northern white rhino eggs suitable for fertilization with banked sperm derived from four deceased males.

The work is described in more detail in the journal Science Advances.