Acetaminophen is the only medication recommended for pain and fever management during pregnancy. However, studies have reported an association between in utero acetaminophen and neurocognitive disorders later in life. Additionally, acetaminophen has been shown to have endocrine disrupting properties altering hormones critical for normal fetal development. As the placenta is an endocrine organ that produces hormones for fetal development, any attempts to elucidate the mechanism underlying in utero acetaminophen and birth outcomes must also focus on the placenta. The present study set out to examine the effect of acetaminophen on mRNA expression, protein expression and hormone synthesis in placental JEG-3 cells. The analysis focused on genes involved in steroidogenesis and acetaminophen metabolism as well those with known roles as nuclear receptors and transporters. The results highlight that at high concentrations, acetaminophen reduced the gene expression of aromatase (CYP19A1) and type 1 3β-hydroxysteroid dehydrogenase (HSD3B1), and increased the expression of 17β-hydroxysteroid dehydrogenase (HSD17B1). Additionally, acetaminophen at high concentrations also reduced the protein expression of aromatase (CYP19A1). These effects were accompanied by a significant dose-dependent decrease in estradiol secretion. Estradiol plays an important role in the development of reproductive organs and the brain of the developing fetus. This study highlights the potential for acetaminophen to interfere with hormone regulation during pregnancy and underscores the need for additional studies aimed at understanding the endocrine disruption activity of acetaminophen during fetal development.

Highlights miRNAs are important epigenetic regulators of placental gene and protein expression. miRNAs play a role in placenta developmental processes such as trophoblast invasion. Placental miRNAs are susceptible to exposure to environmental chemicals. miRNAs are involved in the pathogenesis of pregnancy-related diseases.

No abstract

No abstract