Dynamic changes in leptin distribution in the progression from ovum to blastocyst of the pre-implantation mouse embryo.

The hormone leptin, which is primarily produced by adipose tissue, is a critical permissive factor for multiple reproductive events in the mouse, including implantation. In the CD1 strain, maternally derived leptin from the oocyte becomes differentially distributed among the blastomeres of pre-implantation embryos to create a polarized pattern, a feature consistent with a model of development in which blastomeres are biased toward a particular fate as early as the two-cell stage. In this study, we have confirmed that embryonic leptin is of maternal origin and re-examined leptin distribution in two distinct strains in which embryos were derived after either normal ovulation or superovulation. A polarized pattern of leptin distribution was found in the majority of both CD1 and CF1 embryos (79.1 and 76.9% respectively) collected following superovulation but was reduced, particularly in CF1 embryos (29.8%; P<0.0001), after natural ovulation. The difference in leptin asymmetries in the CF1 strain arose between ovulation and the first cleavage division and was not affected by removal of the zona pellucida. The presence or absence of leptin polarization was not linked to differences in the ability of embryos to normally develop to blastocyst. In the early blastocyst, leptin was confined subcortically to trophectoderm, but on blastocoel expansion, it was lost from the cells. Throughout development, leptin co-localized with LRP2, a multi-ligand transport protein, and its patterning resembled that noted for the maternal-effect proteins OOEP, NLRP5, and PADI6, suggesting that it is a component of the subcortical maternal complex with as yet unknown significance in pre-implantation development.