Physiological role of kallikrein-kinin system in implantation

Abstract

Increased capillary permeability at the site of blastocyst attachment has been shown to be a requisite for implantation in all species. We suggest that B2 receptor which is known to increase blood flow and affect capillary permeability at higher concentrations, is an important embryonic factor involved in the initiation of the implantation process. A differential gene expression screen was employed to identify the genes that regulated by steroid hormones in the uterus during pregnancy. We isolated mRNAs from uteri of ovx-model (E2, P4, and E2 after P4 injection) and delayed implantation model (pregnant day 4 ; ovx and E2 injection) mice. Expressions of Klk 4 and 5 were under the control of estrogen and its receptor. The expression of Klk 1, 2, and Kig 2 was induced by progesterone and ICI 182,780. In the case of Klk 12, its expression was induced by estrogen and by ICI 182,780 and RU 486. Such a curious regulation pattern was also observed in Kig 1 and B2 receptor. In delayed-implantation model mice, the expression of Klk 1 and 2 expressed from 0.5 hr after estrogen administration and dramatically increased from 1.5 hr and stayed the levels. Klk 4, 5 and 6 peaked at 6 hr post estrogen administration. In the case of Klk 12, its expression was dramatically increased at 0.5 hr and decreased continuously after then. Kig 1 and 2 peaked at 0.5 hr and 6 hr, respectively. B2 receptor peaked at 6 hr after implantation induction. The numbers of blood vessel specific sites were decreased by the B2 receptor antagonist. On the other hand, the agonist BK increased the intensity of FITC-dextran in the implantation site. From this study, it is revealed that the factors for kallikrein-kinin system expressed at the stages of periimplantation and stayed under the control of sex steroid hormones. It is suggested that the role of kallikrein-kinin system at the time of implantation may the inducer of angiogenesis and vasodilation.