Regulation of hematopoiesis by pregnancy-specific hormones

Mammalian pregnancy is accompanied by remarkable physiological changes in the mother, including elevated levels of blood cell production. An enhanced hematopoietic output serves to compensate for the dramatic increase in blood volume, reaching 30–50% above normal levels during pregnancy. More important, a higher number of blood cells in the maternal circulation enables efficient transport of nutrients and oxygen to the fetal compartment and removal of metabolic wastes from the developing fetus. Although elevated concentrations of hematopoietic factors likely contribute to the pregnancy-specific alteration of blood cell development, it is possible that cytokines synthesized exclusively during gestation might account for the rapid and reversible changes in hematopoiesis in the mother.; Consistent with this hypothesis, we have identified five new prolactin-like proteins, members of the cytokine superfamily, which are secreted by the mouse placenta during pregnancy. Among these placental hormones, prolactin-like protein-E (PLP-E) and PLP-F target megakaryocytes (MK), hematopoietic cells that give rise to blood platelets. In the mouse, PLP-E enhances MK differentiation and promotes the growth of MK progenitors through a gp130-dependent pathway. Interestingly, although the synthesis of PLP-E is restricted to mouse pregnancy, the PLP-E receptor is present on MK from nonpregnant and male mice, suggesting the PLP-E signaling pathway is likely to play important roles beyond pregnancy. PLP-E also binds to human hematopoietic cells including MK. In combination with thrombopoietin, PLP-E potently increases the expansion of progenitors for multiple myeloid lineages including BFU-E, CFU-GEMM, and CFU-MK, and maintains the proliferative potential of MK progenitors. Therefore, pregnancy-specific placental hormones participate in regulating the adaptation of maternal physiology to pregnancy. Furthermore, this study demonstrates that investigations of placental hormones in experimental animal systems can lead to the discovery of novel factors with important activities in reproduction and development, which potentially may lead to new clinical therapies.