ABO phenotype protected reproduction as it is based on specific fucosylations

Peter Arend
2016 Figshare  
The molecular biological relationship between human fertility and the formation of the ABO(H) blood group phenotype is evident in the rare (Oh) or Bombay blood type, which, based on the history of his own family, the Darwin/Wedgewood Dynasty, Charles Darwin would have interpreted as resulting from reduced fertility in consanguinities. In its native form, the Bombay type occurs in individuals with an extremely rare genotype (h/h;se/se), in whom the fucosyltransferases FUT1 and FUT2 are not
more » ... ed due to point mutations. These enzymes, which are encoded on chromosome 19, are epistatically connected with the A and B allelic glycotransferase functions encoded on chromosome 9, and the fucosyl residues provide the functional-structural basis for the formation of any ABO(H) phenotype on the cell surface or in secretions and plasma proteins. Immunoglobulins are also heavily fucosylated, and fucosyl residues appear, via developmental variations in their positions on cell surfaces and on the heavy chains of immunoglobulins, to increase or reduce antibody-mediated cellular cytotoxicity involving physiological anti-self-reactivity; moreover, by regulating the assembly and intracellular signalling of precursor B cell receptors, the core fucosylation of immunoglobulin heavy chains represents a key mechanism in clonal selection. In fact, the seminal plasma of leukospermic infertile men has been reported to exhibit high levels of poorly core-fucosylated IgG. Thus, when antibody-dependent cellular cytotoxicity can be increased 50-fold simply by removing the single fucose residue from the Fc glycan, in Bombay type individuals, the non-somatic glycosylation processes of embryogenic stem cell-to-germ cell transformation are most likely exposed to metabolic competition with multiple glycosidic sites of poorly fucosylated, glycan-depleted immunoglobulins, suggesting to promote anti-self-reactive cellular cytotoxicity in male gamete performance.
doi:10.6084/m9.figshare.1409398.v362 fatcat:j4qga6fygvgz5nyxmgs5disony