Background: Experimental transplantation studies in mice show that totipotent stem cells (including bone marrow-derived) can established spermatogenesis in a cytotoxin-depleted germinal epithelium. Despite over a million human bone marrow transplants (BMT), it is not known whether bone marrow stem cells when injected intravenously for BMT colonize the human testicular epithelium. No previous studies of sperm genotype after bone marrow transplantation are reported.
Objectives: To differentiate host from donor genotype in sperm of men who have undergone successful BMT.
Materials and Methods: Triplet DNA samples (sperm, blood, hair) obtained from men who had recovered sperm production after BMT were genotyped using 44 autosomal and 3 sex-related single nucleotide polymorphisms to determine the tissue genotype in three pairwise comparisons of DNA profiles.
Results: Participants were 14 men at a median 5.5 years after allogeneic BMT who had a median sperm output of 77 million sperm/ejaculate. In 14/14 the donor (leukocyte) DNA genotype differed significantly from the sperm and hair genotypes whereas hair and sperm genotypes showed no differences
Discussion These data suggest that spermatogenesis and paternity after successful BMT is likely to be of the host and not the donor genetic origins. A healthy blood:testis barrier is the likely explanation of this protection from host stem cell colonization. The small sample size reflects the paucity of eligible man with recovered spermatogenesis after BMT. A large-scale epidemiological analysis of progeny sex ration is proposed to estimate the frequency of bone marrow donor stem cell colonization of the testicular germinal epithelium.
Conclusion: Colonization of the testicular germinal and hair follicle epithelia by allogeneic BMT donor stem cells is rare or does not occur.