Surprising prenatal toxicity of epidermal lipoxygenase-3

•Epidermal lipoxygenase-3 may induce fetal growth restriction and intrauterine death.•We found a lack of glycogen trophoblasts and altered gene expression in the placenta.•Epidermal lipoxygenase-3 metabolites may have an impact on placental development.

Metabolites of the epidermal lipoxygenase-3 (eLOX-3) are involved in various metabolic pathways. Most unexpectedly, intra-amniotic delivery of eLOX-3 to mice at gestational day 14.5, both via an adenoviral vector and as recombinant protein, resulted in fetal growth restriction and intrauterine death. Periodic acid-Schiff staining and RT-PCR analysis of placentae from fetuses exposed to eLOX-3 indicated a lack of glycogen trophoblasts in the junctional zone. Placenta-specific gene expression was altered. Thus, the observed prenatal toxicity of eLOX-3 could be due to a strong effect on placental development.