The Role of Interferon (IFN)-γ in Extravillous Trophoblast Cell (EVT) Invasion and Preeclampsia Progression

Reprod Sci. 2023 May;30(5):1462-1469. doi: 10.1007/s43032-022-01110-x. Epub 2022 Oct 26.

Abstract

The involvement of the immune system in pregnancy is a controversial subject. The functions of T helper (Th) 1 and Th2 cells have been proposed, that Th1 cytokines promoting allograft rejection may impair pregnancy, whereas Th2-type cytokines suppressing Th1 responses improve allograft tolerance and hence embryonic survival. Maternal-fetal tolerance begins in the uterus; therefore, optimal adaptation to the fetus is the result of a complex interference. The invasion of extravillous trophoblast cells (EVTs) into the decidua and the inner third of the myometrium is essential for a healthy pregnancy. The mechanisms that influence trophoblast invasion are unknown; however, cytokines from uterine natural killer (uNK) cells, NKT cells, macrophages, and T cells appear to be involved. All these cells are major sources of interferon gamma (IFN-γ). Recent studies have shown that IFN-γ can inhibit EVT invasion via a mechanism dependent on an increase in EVT apoptosis and a decrease in matrix metalloproteinases (MMPs). Regarding controversies in this context, this study aimed to comprehensively review the role of IFN-γ and IFN-γ-producing cells in EVT invasion, successful pregnancy, and preeclampsia.

Keywords: Cytokine; IFN-γ; Immune system; Pregnancy; Trophoblast.

Publication types

  • Review

MeSH terms

  • Cytokines
  • Decidua
  • Female
  • Humans
  • Interferon-gamma*
  • Interferons
  • Pre-Eclampsia*
  • Pregnancy
  • Pregnancy Trimester, First
  • Trophoblasts / physiology

Substances

  • Interferon-gamma
  • Interferons
  • Cytokines