Research progress on the STAT signaling pathway in pregnancy and pregnancy-associated disorders

Front Immunol. 2024 Jan 3:14:1331964. doi: 10.3389/fimmu.2023.1331964. eCollection 2023.

Abstract

Signal transducer and activator of transcription (STAT) proteins, pivotal regulators of signaling cascades, undergo activation in response to the stimulation of cytokines and growth factors, and participate in biological processes, including inflammation, immune responses, cell proliferation, and differentiation. During the process of pregnancy, STAT signaling is involved in regulating embryonic implantation, endometrial decidualization, and establishing and maintaining maternal-fetal immune tolerance. Increasing evidence suggests that aberrant STAT signaling contributes to the occurrence and development of pregnancy disorders, including repeated implantation failure (RIF), preeclampsia (PE), recurrent spontaneous abortion (RSA), preterm birth (PTB) and gestational diabetes mellitus (GDM). Elucidating the molecular mechanisms of the STAT signaling pathway holds promise for further understanding the establishment and maintenance of normal pregnancy, and thereby providing potent targets and strategic avenues for the prevention and management of ailments associated with pregnancy. In this review, we summarized the roles of the STAT signaling pathway and its related regulatory function in embryonic implantation, endometrial decidualization, and maternal-fetal immune tolerance. In conclusion, in-depth research on the mechanism of the STAT signaling pathway not only enhances our understanding of normal pregnancy processes but also offers STAT-based therapeutic approaches to protect women from the burden of pregnancy-related disorders.

Keywords: maternal-fetal immune tolerance; maternal-fetal interface; pregnancy; pregnancy-related disorders; signal transducer and activator of transcription.

Publication types

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

MeSH terms

  • Abortion, Habitual*
  • Embryo Implantation
  • Female
  • Humans
  • Infant, Newborn
  • Pregnancy
  • Pregnancy Complications*
  • Premature Birth*
  • Signal Transduction

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the National Natural Science Foundation of China (82274575), Major Basic Research Project of Shandong Natural Science Foundation (ZR2023ZD56), the Natural Science Foundation of Shandong Province (ZR2019MH039, ZR2021MH175, ZR2022LZY011), Co-construction project of State Administration of TCM (GZY-KJS-SD-2023-034, GZY-KJS-SD-2023-046), the Project of Science and Technology of traditional Chinese Medicine of Shandong Province (2021Q084), and Taishan Scholars (Tsqn201812125). National Youth Qihuang Scholar Training Program and Shandong Province Traditional Chinese Medicine High Level Talent Cultivation Project.