Work

CD36-mediated arachidonic acid influx from decidual stromal cells increases inflammatory macrophages in miscarriage

Year: 2024

Type: article

Abstract: Spontaneous abortion is associated with aberrant lipid metabolism, but the underlying mechanisms remain unclear. Here, we show that lipids are accumulated in decidual stromal cells (DSCs) and macrophages (dMφs) in women with miscarriage and mouse abortion-prone models. Moreover, we show that excessive lipids from DSCs are transferred to dMφs via a CD36-dependent mechanism that induces inflammation in dMφs. In particular, DSC-derived arachidonic acid (AA) is internalized by dMφs via CD36, which activates cyclooxygenase 2-dependent prostaglandin E2 production and interleukin (IL)-1β expression. In mice, AA injection induces miscarriage, whereas conditional knockout of Cd36 in dMφs ameliorates AA-induced embryo loss. Additionally, DSC-derived prolactin (PRL) inhibits CD36-mediated lipid intake in dMφs, and PRL administration reduces embryo loss in pregnant mice treated with CD36 + Mφs. Our findings reveal a critical interplay between DSCs and dMφs in dysregulated lipid metabolism that may contribute to miscarriage, in which PRL may be harnessed as a therapeutic agent.

Source: Cell Reports

DOI: 10.1016/j.celrep.2024.114881