Restricted spatiotemporal expression of lactoferrin during murine embryonic development

Lactoferrin is a member of the transferrin family of iron-binding glycoprot eins. Lactoferrin is induced by estrogen in the mouse uterus during early p regnancy. However, the expression and function, if any, of lactoferrin in t he preimplantation embryo during this developmental period has not been inv estigated. In the current study, the spatiotemporal expression of lactoferr in during murine embryogenesis was examined using in situ hybridization and immunohistochemical analyses. Lactoferrin expression was first detected in the 2-4 cell fertilized embryo and continued until the blastocyst stage of development. Interestingly, at the 16-cell stage, coinciding with the firs t major differentiation step in the embryo, lactoferrin messenger RNA (mRNA ) is synthesized by the inner cells, whereas the protein is selectively tak en up by the outside cells. This differential pattern of lactoferrin messen ger RNA and protein localization continues until the blastocyst stage, with expression almost absent in the hatched blastocyst. Lactoferrin expression does not resume in the embryo until the latter half of gestation, where it is first detected in neutrophils of the fetal Liver at embryonic day 11.5 and later in epithelial cells of the respiratory and digestive systems. Our results show that lactoferrin is expressed in a tightly regulated spatiote mporal manner during murine embryogenesis and suggest a novel paracrine rol e for this protein in the development of the trophoectodermal lineage durin g preimplantation development.