Palmitic Acid Impedes Extravillous Trophoblast Activity by Increasing MRP1 Expression and Function

Area of Science:

• Reproductive biology
• Cell biology
• Biochemistry

Background:

• Placental extravillous trophoblasts (EVTs) are crucial for fetal development, mediating uteroplacental vascular remodeling.
• Adequate folate levels are essential for EVT proliferation and invasion, impacting fetal oxygen and nutrient supply.
• Multidrug resistance-associated protein 1 (MRP1) is an efflux transporter that removes folate from EVTs.

Purpose of the Study:

• To investigate the hypothesis that palmitic acid enhances MRP1-mediated folate removal from EVTs, thus disrupting placental vascular remodeling.
• To elucidate the role of palmitic acid and MRP1 in regulating EVT function.

Main Methods:

• Human first-trimester EVT cell lines (HTR-8/SVneo and Swan-71) were treated with palmitic acid.
• Gene and protein expression of MRP1 (ABCC1) were analyzed.
• Folate efflux, cell migration, and invasion assays were performed.
• Experiments included treatment with N-acetylcysteine (NAC) and use of an ABCC1 knockout cell line.

Main Results:

• Palmitic acid significantly increased ABCC1 gene and MRP1 protein expression in EVTs.
• Increased folate efflux correlated with decreased EVT migration and invasion.
• NAC treatment reversed palmitic acid-induced MRP1 upregulation and restored EVT function.
• ABCC1 knockout cells exhibited enhanced migration and invasion.

Conclusions:

• Palmitic acid promotes MRP1-mediated folate efflux from EVTs, impairing their vascular remodeling function.
• This mechanism provides a link between maternal saturated fatty acid intake and compromised fetal development.
• Targeting MRP1 or using antioxidants like NAC may offer therapeutic potential for mitigating adverse effects.