Perfluorooctanoic acid induces transcriptomic alterations in second trimester human cytotrophoblasts

Area of Science:

• Environmental Health
• Toxicology
• Reproductive Biology

Background:

• Poly- and perfluoroalkylated substances (PFAS) are persistent industrial chemicals found globally in human tissues.
• Prenatal exposure to PFAS, including perfluorooctanoic acid (PFOA), is linked to adverse pregnancy outcomes, but underlying mechanisms are unclear.
• Emerging research suggests PFAS may target the placenta and impair trophoblast function.

Purpose of the Study:

• To investigate the effects of PFOA on cytotoxicity and gene expression in human cytotrophoblasts (CTBs).
• To identify specific molecular pathways affected by PFOA in placental cells.

Main Methods:

• Primary human second-trimester CTBs were cultured and exposed to varying concentrations of PFOA.
• Cell viability was assessed after 24 hours.
• Transcriptome analysis was performed to identify gene expression changes.
• In silico analyses were used to predict regulatory pathways.

Main Results:

• PFOA significantly reduced CTB viability and induced cell death in a concentration-dependent manner.
• Subcytotoxic PFOA concentrations altered the expression of hundreds of genes.
• Affected genes included those involved in lipid metabolism and innate immune responses (e.g., CRH, IFIT1, TNFSF10).
• In silico analysis implicated peroxisome proliferator-activated receptor (PPAR) pathways.

Conclusions:

• PFOA directly impacts human cytotrophoblast viability and alters critical gene expression pathways.
• These findings suggest a mechanism by which PFOA could contribute to placental dysfunction and adverse pregnancy outcomes.
• Further research into PFOA's effects on placental health is warranted.