Hyperglycemia disturbs trophoblast functions and subsequently leads to failure of uterine spiral artery remodeling

Front Endocrinol (Lausanne). 2023 Apr 5:14:1060253. doi: 10.3389/fendo.2023.1060253. eCollection 2023.

Abstract

Uterine spiral artery remodeling is necessary for fetal growth and development as well as pregnancy outcomes. During remodeling, trophoblasts invade the arteries, replace the endothelium and disrupt the vascular smooth muscle, and are strictly regulated by the local microenvironment. Elevated glucose levels at the fetal-maternal interface are associated with disorganized placental villi and poor placental blood flow. Hyperglycemia disturbs trophoblast proliferation and invasion via inhibiting the epithelial-mesenchymal transition, altering the protein expression of related proteases (MMP9, MMP2, and uPA) and angiogenic factors (VEGF, PIGF). Besides, hyperglycemia influences the cellular crosstalk between immune cells, trophoblast, and vascular cells, leading to the failure of spiral artery remodeling. This review provides insight into molecular mechanisms and signaling pathways of hyperglycemia that influence trophoblast functions and uterine spiral artery remodeling.

Keywords: Hofbauer cells; decidual NK cells; hyperglycemia; trophoblast; uterine spiral artery remodeling.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arteries
  • Female
  • Humans
  • Hyperglycemia* / complications
  • Hyperglycemia* / metabolism
  • Placenta / physiology
  • Placenta Growth Factor / metabolism
  • Pregnancy
  • Trophoblasts* / metabolism

Substances

  • Placenta Growth Factor

Grants and funding

This research was funded by grants from the National Key Research and Development Program of China (2018YFC1002800), the Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210202), the National Natural Science Foundation of China (81401274, 81971403 and 82171669), the Shanghai Jiao Tong University Trans-Med Awards Research (20210201), and Funds for Outstanding Newcomers, Shanghai Sixth People’s Hospital (X-3664), the Shanghai Science and Technology Commission (22dz1202303).