The protective effect of maternal electroacupuncture on prenatal nicotine exposure-induced intrauterine growth restriction in rats by improving placental angiogenesis

TL;DR

Maternal electroacupuncture can help prevent fetal growth issues caused by nicotine exposure during pregnancy by improving placental blood vessel growth in rats.

Contribution

This study shows that electroacupuncture reverses nicotine-induced IUGR by enhancing placental angiogenesis via the PGF/VEGFR-1/PI3K/AKT pathway.

Findings

EA restored fetal and placental growth parameters and improved placental perfusion in nicotine-exposed rats.

EA increased placental vascular density and upregulated key angiogenic genes like PGF and VEGFR-1.

Transcriptomic analysis confirmed EA's activation of the PI3K/AKT signaling pathway in placental tissue.

Abstract

Fetal intrauterine growth restriction (IUGR) is a common pregnancy complication that significantly impacts fetal health and long-term outcomes. Prenatal nicotine exposure (PNE) is a major environmental risk factor for IUGR, with abnormal placental angiogenesis, leading to insufficient placental perfusion, which represents a key pathological process. Electroacupuncture (EA), a non-pharmacologic traditional Chinese medicine therapy, is known to regulate qi and blood flow and improve circulation. This study investigated whether EA could reverse PNE-induced IUGR by enhancing placental angiogenesis and explored the underlying mechanisms. In a PNE-induced IUGR rat model, daily EA treatment was applied at bilateral “ST36” acupoints. On gestational day 20, fetal and placental growth parameters, along with placental perfusion, were assessed. Placental RNA sequencing (RNA-seq) was performed to identify relevant biological pathways, with key pathway molecules validated by qRT-PCR and Western blot. EA significantly restored fetal weight and length and increased placental weight and diameter. It also reduced the umbilical artery resistance index and improved placental perfusion. Furthermore, EA increased placental vascular density. Bulk RNA-seq revealed EA induced substantial changes in placental gene expression, including significant upregulation of the key angiogenic factor placental growth factor (PGF). Gene Ontology (GO) enrichment analysis indicated that differentially expressed genes were primarily involved in stress response regulation and cell surface receptor-mediated signal transduction, with notable enrichment in the PI3K/AKT signaling pathway. These transcriptomic findings were validated by qRT-PCR and Western blot, which confirmed that EA upregulated the mRNA expression of PGF, VEGFR-1, PI3K, and AKT, and increased the protein levels of PGF, VEGFR-1, and the phosphorylation of PI3K/AKT (p-PI3K, p-AKT). This integrated evidence suggests that maternal EA treatment may promote placental angiogenesis via activation of the PGF/VEGFR-1/PI3K/AKT pathway, thereby protecting against PNE-induced IUGR.

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