Immunoregulation of the decidualization program: focus on the endoplasmic reticulum stress

Area of Science:

• Reproductive biology
• Cellular stress responses
• Immunology

Background:

• Decidualization involves endometrial stromal cell reprogramming, cytokine/chemokine secretion, and immune cell recruitment.
• This process alters the endometrial secretome, producing immunomodulatory factors.
• Increased protein secretion during decidualization is linked to physiological endoplasmic reticulum (ER) stress and the unfolded protein response (UPR).

Purpose of the Study:

• To review the association between ER stress, UPR, and decidualization.
• To explore the role of these processes in embryo implantation and pregnancy outcomes.
• To discuss how ER stress and UPR alterations may contribute to pregnancy complications.

Main Methods:

• Review of existing literature on ER stress, UPR, decidualization, and implantation.
• Analysis of signaling pathways connecting ER stress, inflammation, and angiogenesis.
• Examination of the NLRP3 inflammasome activation and IL-1β maturation in decidualization.

Main Results:

• ER stress and UPR are integral to decidualization, supporting protein folding and secretion.
• ER stress activates the NLRP3 inflammasome, leading to IL-1β maturation with pro-implantatory effects.
• Proper regulation of sterile inflammation is essential for a tolerogenic pregnancy environment.

Conclusions:

• ER stress and UPR are vital for successful embryo implantation and placentation.
• Altered ER stress and UPR signaling can result in recurrent implantation failures, pregnancy loss, or preeclampsia.
• Understanding these pathways offers insights into managing pregnancy complications.