CELL BIOLOGY SYMPOSIUM: perspectives: possible roles of polymorphonuclear neutrophils in angiogenesis and lymphangiogenesis in the corpus luteum during development and early pregnancy in ruminants.

The establishment of pregnancy requires well-balanced regulation of the endocrine and immune systems and involves interactions among the conceptus, oviduct-uterus, and corpus luteum (CL). In particular, a rapid increase in plasma progesterone during the first week after ovulation is critical for the growth of the conceptus and successful pregnancy in cattle. Events involved in maternal recognition of pregnancy (MRP) may commence within 1 wk from AI, when interferon-stimulated gene expression in circulating polymorphonuclear neutrophils (PMN) increases in pregnant cows. To regulate optimal endocrine conditions within this time, the CL must develop rapidly, with active angiogenesis and lymphangiogenesis. The major angiogenic factors, vascular endothelial growth factor and fibroblast growth factor 2, contribute to the development of the CL but may also act as chemoattractants for PMN. Indeed, the number of PMN is greatest in the new CL, where PMN together with IL-8 induce active angiogenesis and lymphangiogenesis. During MRP, the conceptus secretes interferon tau (IFNT), which prevents CL regression by inhibiting luteolytic release of PGF(2 alpha) from uterine endometrium. In addition, IFNT and PGE(2) reach the CL and may contribute to desensitizing the CL to the luteolytic effects of PGF(2 alpha). In the bovine CL, lymphangiogenesis, stimulated by IFNT, may occur during MRP, and thus a shift of local immunity might occur at this timing. The aforementioned evidence supports the possible involvement of PMN in the establishment of pregnancy via CL regulation. Further investigation could expand our understanding of the communication between zygotes, PMN, and reproductive organs during early pregnancy. This should provide new insight into the contribution of neutrophils to CL function and immune tolerance during early pregnancy in ruminants.