Transmission of Y chromosomes from XY female mice was made possible by the replacement of cytoplasm during oocyte maturation.

Abstract

The B6.Y(TIR) sex-reversed female mouse is anatomically normal at young ages but fails to produce offspring. We have previously shown that its oocytes go through the meiotic cell cycle up to the second metaphase; however, the meiotic spindle is not properly organized, the second meiotic division goes awry after activation or fertilization, and none of the oocytes initiate embryonic development. In the present study, we transferred the nuclei of GV-stage oocytes from XY females into the enucleated GV-stage oocytes from (B6.DBA)F1.XX females. The resultant reconstructed oocytes properly assembled second meiotic spindles after in vitro maturation and produced healthy offspring after in vitro fertilization. Some male pups inherited maternal Y chromosomes. We conclude that the cytoplasm of the XY oocyte is insufficient to support spindle formation at the second metaphase whereas its replacement with the cytoplasmic material from an XX oocyte allows normal development.