Placental transcriptomic profiling in a mouse model of fetal growth restriction reveals disturbed inflammation and immunity regulation†.

Abstract

To date, few studies have specifically explored the placental transcriptome of an animal model of fetal growth restriction (FGR) with nitric oxide (NO) deficiency. The aim of this study was to use NG-nitro-L-arginine methyl ester (L-NAME) to establish a mouse model of FGR with NO deficiency, and explore the histological changes and the transcriptomic complexity of the placenta. We established a FGR mouse model via L-NAME administration (n = 6 per group). We assessed the biometric phenotypes of the fetuses and the placentas, and analyzed placental and cellular morphology to confirm the pathological changes that occur in FGR placentas. Finally, we applied RNA-seq to analyze the placental transcriptome from the L-NAME-induced mouse model of FGR. We established a mouse model of FGR using L-NAME with biometric and pathological changes. Transcriptomic analysis identified eight differentially expressed genes (DEGs) between the FGR-affected and normal placentas, including six upregulated genes (solute carrier family 6 (neurotransmitter transporter), member 14 (Slc6a14), matrix metallopeptidase 9 (Mmp9), RAS guanyl releasing protein 1 (Rasgrp1), ATP-binding cassette, sub-family B member 1B (Abcb1b), solute carrier family 16 (monocarboxylic acid transporters), member 12 (Slc16a12), and transmembrane protein 255A (Tmem255a)) and two downregulated genes (protein tyrosine phosphatase receptor type N polypeptide 2 (Ptprn2) and meiosis 1 associated protein (M1ap)). These DEGs are highly involved in angiogenesis, the immune system, and inflammatory signaling pathways, underscoring the multifaceted nature of FGR pathology. This study contributes to the understanding of FGR pathophysiology, emphasizing the importance of the immune-related molecular markers and offering potential targets for therapeutic intervention.