SummaryThe present study was conducted to determine whether the chromosomal aberrations accompanied by production of transgenic rabbit could transmit through generations or abnormal cells are apparently eliminated through offspring. Two lines of transgenic and non-transgenic offspring (F4 generation), each from the same litters were produced by breeding transgenic females with non-transgenic male (line I) and transgenic females with transgenic male (line II). Altogether 5 transgenic and 3 non-transgenic rabbits from line I and 5 transgenic and 2 non-transgenic rabbits from line II, of about 9 months old were analyzed. Transgenic rabbits were produced in F0 generation by microinjection of mWAP-hFVIII gene construct into male pronucleus of fertilized eggs from superovulated New Zealand white or Californian rabbits. Samples from bone marrow cells were collected from transgenic and non-transgenic rabbits for chromosomal analysis. The results indicated that, the frequencies of chromosomal abnormalities increased significantly (pϽ0.01) in the fourth generations of transgenic rabbits expressing recombinant human clotting Factor VIII in their mammary gland. Both numerical aberrations as polyploidy and structural aberrations as fragments, deletion, centromeric attenuations and chromatid gaps were recorded. The percentage of chromosomal aberrations in transgenic F4 offspring was 2.61% for numerical and 3.37% for structural ones. Polyploidy and fragments were more frequent types of aberrations that were reported in bone marrow cells of all examined rabbits. It is concluded that, chromosomal abnormalities were transmitted to the fourth generation of transgenic rabbit offspring by low percentage. So, it will be necessary to use cytogenetic analysis for eliminating any animal with chromosomal aberrations and this will help in selecting the optimal lines for dissemination.