Microcystin-LR prenatal exposure induces coronary heart disease through macrophage polarization imbalance mediated by trophoblast-derived extracellular vesicles.
Sci Total Environ
; 948: 174979, 2024 Oct 20.
Article
en En
| MEDLINE
| ID: mdl-39053546
ABSTRACT
Microcystin-leucine arginine (MC-LR) has been reported to exhibit placental toxicity, leading to potential adverse pregnancy outcomes. Placental abnormalities often coincide with congenital heart defects (CHD). However, the extent to which MC-LR-induced placental abnormalities contribute to CHD and the cellular mechanisms underlying this association remain unknown. In this study, we observed abnormal polarization of placental macrophages in pregnant mice exposed to MC-LR during pregnancy, and the embryos developed cardiac developmental defects that persisted into adulthood. Trophoblast-derived extracellular vesicles (T-EVs) increase in number during pregnancy and act as a critical signal in macrophage polarization. However, MC-LR significantly affected the miRNA expression profile of T-EVs. Upon internalization into macrophages, T-EV-derived miR-377-3p specifically targets the 3'UTR region of NR6A1 to inhibit gene expression. Silencing of transcription suppressor NR6A1 leads to abnormal activation of the downstream mTOR/S6K1/SREBP pathway, inducing metabolic reprogramming and ultimately leading to M1 polarization of macrophages. This study elucidated the placental mechanism underlying MC-LR-induced CHD for the first time, providing insights into the environmental risks associated with CHD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trofoblastos
/
Microcistinas
/
Vesículas Extracelulares
/
Macrófagos
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Sci Total Environ
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos