Supplementation with hArg During the Rapid Growth of the Placenta Modulates Final Placental Angiogenesis and Pregnancy Outcomes.

BACKGROUND: Placental angiogenesis is crucial for ensuring placental function and normal fetal development. It has been demonstrated that elevated plasma levels of homoarginine (hArg), an endogenous amino acid, during pregnancy correlate with enhanced vascular endothelial function. However, the effect of hArg in placental angiogenesis during pregnancy is still ambiguous. This study seeks to evaluate the impact of supplemental hArg during the rapid placental growth phase in early pregnancy, a key moment for placental angiogenesis, on ultimate pregnancy outcomes and placental angiogenesis in rats, as well as its potential processes. METHODS: This study utilized thirty 8-week-old female Sprague Dawley rats as pregnant animals, which were randomly allocated to control and treatment groups (15 per group) and administered 20 mg/kg of hArg from embryonic day 0.5 (E0.5) to E13. The dams were euthanized on E21. RESULTS: Maternal hArg dietary supplementation positively influenced pregnancy outcomes, resulting in a significant increase in the number of live-born offspring and total placental weight, alongside elevated maternal circulating reproductive hormone levels. Additionally, the upregulation of the amino acid transporter in the placenta of the treatment group established a basis for hArg accumulation in the placenta, hence promoting hArg-specific augmentation of eNOS-mediated NO production. The treated group simultaneously demonstrated an expanded labyrinthine zone, increased blood sinusoids area, enhanced vascular density, and raised levels of proangiogenic factors. Mechanistically, hArg enhanced the expression of proteins linked with the PI3K/AKT signaling pathway. CONCLUSIONS: Supplementation with hArg during the placenta's rapid growth phase enhances placental angiogenesis, ultimately enhancing pregnancy outcomes. This effect may be attributed to the regulation of the PI3K/AKT signaling pathway.