The role of genotype, genomic imprinting, and sex hormones in platelet and megakaryocyte production.

Our previous data suggested that the higher average ploidy of C3H mouse megakaryocytes is the result of interaction of multiple alleles that act in an additive fashion. Average megakaryocyte DNA content increased with the proportion of C3H genotype. Other factors also influence megakaryocyte ploidy; male mice had megakaryocytes of higher ploidy than did female mice, and the genes that determine megakaryocyte ploidy had a differential expression, depending on the sex of the parent, a finding that suggests genomic imprinting. The role of genotype (and, thus, megakaryocyte DNA content) on other parameters of platelet production and megakaryocytopoiesis has not been examined. Therefore, we report the effects of genotype on platelet counts, platelet sizes, percent 35S incorporation into platelets, total circulating platelet counts (TCPC), total circulating platelet masses (TCPM), megakaryocyte size and number, and total megakaryocyte masses (TMM). Platelet counts of male mice were inversely related to the proportion of C3H genotype. In other words, male mice with a higher proportion of C3H genotype had lower platelet counts than did male mice with predominantly C57BL genotype (p = 0.04). None of the other platelet production indices were significantly correlated with the C3H genotype content of the offspring. However, a significantly positive correlation (p < 0.0001 for males and p < 0.003 for females) was found between megakaryocyte size and megakaryocyte ploidy. Although no significant difference in megakaryocyte numbers was noted, TMM of male mice was positively correlated (p < 0.05) with megakaryocyte ploidy. Male mice had higher platelet counts, percent 35S incorporation into platelet values, TCPC, and TCPM than did female mice, but platelet sizes were the same for both sexes. Megakaryocyte sizes, numbers, and TMM were higher in male than female offspring of some matings, but in several cases, sex did not appear to affect these parameters. Previous work has shown that this difference in platelet production capabilities due to sex of the mouse is most likely caused by male sex hormones. Evidence of different genetic expression (genomic imprinting), depending on the sex of the parent, was found in platelet counts and TCPC of certain backcrosses of female mice and in platelet sizes of male mice (p < 0.05). Therefore, we show that genotype, male sex hormones, and genomic imprinting influence platelet production in mice, but platelet counts of male mice were negatively correlated with size and DNA content of megakaryocytes.