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Circulating cathepsin B and D in pregnancy

Abstract The purpose of this prospective study was to investigate the changes in the circulating levels of cathepsin B and D in pregnancy. We obtained longitudinal cathepsin B and D levels in 76 healthy pregnant women in the first and third trimesters and compared these levels with 20 non-pregnant controls. The plasma levels of soluble cathepsin B and D were measured using an enzyme-linked immunosorbent assay kit. The cathepsin D concentrations in the third trimester were significantly higher than that in the first trimester (p < .001), and the cathepsin D levels in the first trimester were significantly lower than that in the non-pregnant controls (p = .002). However, there was no significant difference in the cathepsin B level throughout pregnancy compared to the non-pregnant controls. Our study is unique in evaluating the longitudinal changes in the cathepsin B and D levels in pregnancies without obstetric complications. The results implicate that changes in the levels of cathepsins might be essential in placentation. Therefore, molecular and genetic studies on cathepsin B and D are needed to understand the roles of these enzymes in pregnancy, thereby contributing to the understanding of placentation. Impact statement What is already known? Matrix metalloproteinases (MMP) have been widely studied, and their function is very important in the normal implantation process. The level of MMP-9 is known to increase throughout pregnancy, while the level of MMP-2 decreases in the first trimester. In addition to MMPs, other proteases are important for placental development; cathepsins B and D are two of the proteases that are involved in the normal placentation process. The function of cathepsin D is related to MMPs because this protease can activate MMPs either directly or indirectly. Nevertheless, the role of circulating cathepsins in pregnancy has not yet been fully elucidated. What do these results add? This study provides evidence, for the first time, that there are fluctuations of plasma cathepsin D level and there are no changes in the plasma cathepsin B level in a normal pregnancy. Moreover, we demonstrated that a cathepsin D level is significantly decreased in the first trimester compared to the non-pregnant controls, and that the level is markedly elevated in the third trimester. What are the implications of these findings for clinical practice and/or further research? Cathepsins B and D should be further studied locally in the placenta to explain the differences in the concentration of cathepsin D and no changes in cathepsin B, thereby exploring their exact roles.