BIRTH OF NORMAL MICE AFTER REMOVAL OF THE SUPERNUMERARY MALE PRONUCLEUS FROM POLYSPERMIC ZYGOTES

Each year, would wide, tens of thousands of zygotes derived from the i n-vitro insemination of human oocytes undergo polyspermic fertilizatio n. These embryos must presently be discarded because it has never been demonstrated in any mammal that polyspermic zygotes can develop norma lly to term after removal of the supernumerary male pronucleus, Our st udy was undertaken to test the developmental potential of polyspermic zygotes corrected by micromanipulation. Mouse oocytes were inseminated zona-free, and polyspermic zygotes were manipulated so as to remove o ne of the two male pronuclei. Surviving embryos were then observed for further development in vitro and after transfer into pseudopregnant f emales. Of 58 zygotes manipulated, 18 developed to the blastocyst stag e and were transferred, Five animals (two male and three females) were born. The agouti coat colour marker confirmed the genotypes of the ga metes. All five animals developed to normal-appearing adults, and all five produced at least 10 normal offspring. One adult founder animal w as karyotyped and found to have a normal chromosome complement, These results demonstrate for the first time that a mammalian egg that has u ndergone polyspermic fertilization can develop normally after restorat ion of the diploid state by micromanipulation. Accordingly, the result s provide impetus for attempting to rescue polyspermic human embryos.