engleski

The Role of Osteopontin in Early Pregnancy

The uterus is a mucosal tissue that undergoes massive steroid-hormone promoted remodeling during pregnancy to support conceptus survival and development. These changes are accompanied by the differentiation and proliferation of a unique, transient uterine natural killer (uNK) cell lineage. In the human, rat and mouse uterus, uNK cells are terminally differentiated cells reaching their highest numbers in mid gestation and are specifically recruited to placental attachment sites where intensive formation of new maternal blood vessels take place. The robust vascular development that occurs during implantation and early placentation is of paramount importance for the development of a receptive endometrium suitable for implantation. It is known that mouse uNK cells express angiogenic molecules, and we found that sialoprotein osteopontin (OPN) is made by granulated (uNK) cells.Osteopontin (OPN) is a secreted extra cellular protein involved in many physiological and pathological processes including vascular remodeling. OPN is expressed during early pregnancy, and OPN null mice manifest decreased pregnancy rates during midgestation when compared with wild-type counterparts. Differentiation of endometrial stromal cells and formation of new maternal blood vessels at the time of embryo implantation are critical processes for the establishment and maintenance of gestation. In non-immune cells OPN signals mainly trough αvβ3 integrin, and in immune cells trough CD44.αvβ3 has been shown to be highly expressed at the time of embryo attachment, and aberrant expression of αvβ3 is associated with infertility.We hypothesized that OPN/αvβ3 signaling mechanisms control of the angiogenic factors important for the vascularization process during early pregnancy. To test this hypothesis mouse and human uterine tissues were used. Our results suggest that that OPN paracrine signaling pathway significantly contributes to angiogenesis during early pregnancy.

pregnancy; uNK; osteopontin; angiogenesis

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