Flexible adaptation of male germ cells from female iPSCs of endangered Tokudaia osimensis

Abstract

Tokudaia osimensis exhibits high sexual plasticity, through which female somatic cells can be converted to male germline cells.

Applying iPSCs for Preserving Endangered Species and Elucidating the Evolution of Mammalian Sex Determination

“…Therefore, we aim to derive sperm and oocytes from T. osimensis iPSCs in vivo or in vitro and to produce preimplantation embryos using assisted reproductive technology. We have shown that T. osimensis iPSCs exhibit true naïve pluripotency . It is well known that female naïve ESCs express the Xist mRNA from both X chromosomes .…”

“…However, T. osimensis has renounced its Y chromosome and has evolved to generate males (and sperm) without Y‐related genes . Recently, we have shown that female (XO) T. osimensis cells have the potential to generate spermatids in the mouse testicular environment, which suggests the acquisition of sexual plasticity in T. osimensis germ cells via their evolution . In general, mammalian sex determination is regulated by genetics.…”

“…The chimeric contribution in a xenogeneic environment other than that of the mouse and rat is very restricted . Although a cohort of about 40 PGCs is first identifiable at 6.25–7.25 dpc in the mouse, the germline contribution of T. osimensis iPSCs as spermatocytes (0.031%) and oocytes (0.29%) in a xenogeneic environment is severely restricted . In fact, germline differentiation hardly occurs in the xenogeneic (mouse and rat) environment .…”

“…Because of its unique sex chromosome composition, XO/XO, female T. osimensis iPSCs could contribute and survive as germ cells in adult interspecific ovaries and testes, which suggests the acquisition of sexual plasticity by germ cells according to their unique position in evolution (Figure ). Although the candidate regulator(s) affecting the sex determination of T. osimensis have not been elucidated, it is assumed that one of the best ways to study sex determination in this species is the analysis of the exact time point at which the discrimination of the sexes has just occurred.…”

iPSCs from an Endangered Mammalian Species Could Elucidate the Mechanism of Sex Determination with Evolutionary Y Chromosome Loss

“…As this species is gravely endangered, sacrificing any animal for experimental purposes should be avoided. Honda et al have generated true naïve iPSCs from tail biopsy of female T. osimensis , and produced interspecific chimeras by injecting the iPSCs into mouse blastocysts. Although the iPSCs differentiated into both male and female germ cells in chimeric testes and ovaries, respectively, their contributions were severely restricted, probably due to immunological or interspecific incompatibility between T. osimensis germ cells and host gonadal somatic cells.…”