In utero perfluorooctane sulfonate exposure causes low body weights of fetal rats: A mechanism study

•PFOS inhibits rat placental 11β-hydroxysteroid dehydrogenase 2.•PFOS increases corticosterone level in fetal serum after in utero exposure.•PFOS alters placental gene expressions related to nutrition transportation.

ObjectivesThe objective of the present study is to investigate the mechanism of perfluorooctane sulfonate-induced low body weight of fetus by analysis of glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase 2 and gene expression profiling of the placenta after in utero PFOS exposure.Study designPregnant Sprague–Dawley dams were gavaged with 0, 5, and 20 mg/kg body weight PFOS daily from gestational day 12–18. On gestational day 18, pregnant dams were euthanized, placentas, and fetuses were collected.Main outcome measuresBody weights of fetuses and placentas were measured, the corticosterone levels in fetal serum, and 11β-hydroxysteroid dehydrogenase 2 as well as the placental gene profiling were analyzed.Results20 mg/kg PFOS significantly reduced fetal body weight and placental weight. Both 5 and 20 mg/kg PFOS increased fetal serum corticosterone levels. PFOS potently inhibited placental 11β-hydroxysteroid dehydrogenase 2 activity. Of 21,910 genes, 45 genes were significantly downregulated ≥2 fold by 20 mg/kg PFOS, including extracellular matrix (Slpi and Pi16), growth factors and hormones (Trh and Pdf), ion transporters (Aqp1, S100a4, and Abp1), signal transducers (Kap and Ampd3), and structural constituents (A2m and Des).ConclusionsPFOS exposure may alter placental development and function, causing intrauterine growth restriction via inhibiting placental 11β-hydroxysteroid dehydrogenase 2.