Temporal changes in cyclinD-CDK4/CDK6 and cyclinE-CDK2 pathways: implications for the mechanism of deficient decidualization in an immune-based mouse model of unexplained recurrent spontaneous abortion

Mol Med. 2022 Sep 1;28(1):100. doi: 10.1186/s10020-022-00523-3.

Abstract

Background: Deficient endometrial decidualization has been associated with URSA. However, the underlying mechanism is poorly understood. This study aimed to investigate the temporal cytokine changes and the involvement of CyclinD-CDK4/6 and CyclinE-CDK2 pathways in the regulation of the G1 phase of the cell cycle during decidualization in a murine model of URSA.

Methods: Serum and decidual tissues of mice were collected from GD4 to GD8. The embryo resorption and abortion rates were observed on GD8 and the decidual tissue status was assessed. In addition, PRL, Cyclin D, CDK6, CDK4, Cyclin E, CDK2 expression in mice were measured.

Results: URSA mice showed high embryo resorption rate and PRL, Cyclin D, Cyclin E CDK2, CDK4, CDK6 down-regulation during decidualization. The hyperactivated Cyclin D-CDK4/CDK6 and cyclin E/CDK2 pathways inhibit the decidualization process and leading to deficient decidualization.

Conclusion: Insufficient decidualization is an important mechanism of URSA. which is related to the decrease of Cyclin D、Cyclin E、 CDK2、CDK4 and CDK6 in decidualization process of URSA.

Keywords: Cell cycle; Decidualization; Unexplained recurrent spontaneous abortion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual*
  • Animals
  • Cyclin D
  • Cyclin E* / genetics
  • Cyclin E* / metabolism
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase 6 / genetics
  • Cyclins / metabolism
  • Disease Models, Animal
  • Embryo Loss
  • Female
  • Humans
  • Mice
  • Pregnancy

Substances

  • Cyclin D
  • Cyclin E
  • Cyclins
  • CDK2 protein, human
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6