Microcystin-LR inhibits early pregnancy by impairing the vascular network of luteum: Involvement of the MEK/ERK/SP1/VEGFR2 axis.
Food Chem Toxicol
; 170: 113454, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-36206955
ABSTRACT
Microcystin-leucine-arginine (MC-LR) reduces the fertility of female mice, but the mechanism is unknown. We studied the effect of MC-LR on early pregnancy and elucidated its possible mechanism. The number of embryo beds and embryo volume decreased in pregnant mice at 6 or 8 days after fertilization after acute exposure to MC-LR. The corpus luteum secretes estrogen and progesterone, which are involved in embryo implantation and maintenance of early pregnancy. MC-LR exposure reduced luteal blood vessel branches and inhibited hormone synthesis. Functional blood vessels are essential to the maintenance of luteal structure and function. Reduced migration and tube-forming were also detected in human umbilical vascular endothelial cells (HUVECs) treated with MC-LR. MC-LR significantly decreased the expression of vascular endothelial growth factor receptor 2 (VEGFR2) in vivo and in vitro, which was responsible for the inhibited construction of the vascular network. The MEK/ERK/SP1 signal pathway mediated the decrease in VEGFR2 expression, and the agonists of phosphorylated extracellular regulated protein kinases (p-ERK) alleviated the anti-angiogenic effect of MC-LR. In conclusion, we demonstrated the toxicity of MC-LR on construction of vascular network in corpus luteum, which could provide a new perspective on female infertility or miscarriage caused by environmental factors.
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MEDLINE
Assunto principal:
Receptor 2 de Fatores de Crescimento do Endotélio Vascular
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Microcistinas
Idioma:
En
Ano de publicação:
2022
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Article