Language
English
Publication Date
2-18-2026
Journal
Biology of Reproduction
DOI
10.1093/biolre/ioaf198
PMID
40891509
PMCID
PMC12927713
PubMedCentral® Posted Date
2-24-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
Decidualization is the transformation of endometrial stromal cells into functionally specialized cells during the early stages of pregnancy. Occurring in mammals that develop invasive hemochorial placentae, decidualization is a pivotal evolutionary adaptation in mammals that supports pregnancy establishment, implantation, and placentation in a limited number of animal species. During decidualization, an endometrial stromal cell undergoes profound genetic, epigenetic, and proteomic changes, allowing it to prevent immunological rejection and fostering the development of a newly implanted embryo. To tolerate the cellular reprogramming that occurs during decidualization, a stromal cell must withstand reactive oxygen species (ROS), inflammation, and oxidative stress associated with this process. This review focuses on key events that have allowed decidualization to tolerate high levels of oxidative stress during early pregnancy, creating a specialized maternal-fetal interface and allowing for deep placentation. We focus on the features that allowed certain eutherian mammals to develop strong, progesterone (P4)-driven decidualization that resists antioxidant stress and confers cellular resilience. We also discuss how these oxidative stress responses are implicated in reproductive disorders such as endometriosis and recurrent pregnancy loss, underscoring their clinical relevance. We examine known molecular players that work to collectively mitigate oxidative stress from ROS and we highlight the emerging roles of SLC40A1 and GPX4 in coordinating iron balance and mitigating lipid peroxidation to enhance endometrial decidualization. By highlighting the key mechanistic adaptations of endometrial stromal cells at the maternal-fetal interface, we emphasize the importance of mitigating oxidative stress for successful pregnancy establishment and reproductive health.
Keywords
Female, Oxidative Stress, Animals, Humans, Stromal Cells, Pregnancy, Endometrium, Decidua, Reactive Oxygen Species, Embryo Implantation, Decidualization, Oxidative stress, Reactive oxygen species, SLC40A1, GPX4, Endometriosis, Early Pregnancy Loss, Infertility
Published Open-Access
yes
Recommended Citation
Rupak Thapa and Diana Monsivais, "Mechanisms Driving Resistance to Oxidative Stress During Endometrial Stromal Cell Decidualization" (2026). Faculty, Staff and Students Publications. 8181.
https://digitalcommons.library.tmc.edu/baylor_docs/8181
Graphical Abstract