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.

Keywords:

• Cathepsin B
• cathepsin D
• pregnancy

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and the writing of the paper.