The alpha‐tocopherol transfer protein regulates vitamin E transport across placental cell monolayers (758.1)

Abstract

Oxidative stress is thought to cause/ play critical causative role in the etiology of pregnancy disorders such as pre‐eclampsia, intrauterine growth restriction and repeated miscarriages. Vitamin E is a major lipid soluble chain breaking antioxidant that is essential for fetal development. The alpha‐tocopherol transfer protein (TTP) is the only specific regulator of vitamin E homeostasis in vertebrates, which is expressed in liver, brain and placenta. We hypothesized that mother‐fetus transport of vitamin E across the placenta is mediated and regulated by TTP. To test this hypothesis, we used the human choriocarcinoma cell‐line BeWo cultured as monolayers on transwells. Monolayer formation was confirmed by histological evaluation and electric resistance measurements. Trans‐epithelial resistance ranged between 90‐120 Ohms, indicating functional tight junctions throughout the monolayer. Anti‐ E cadherin staining indicated the manolayers converted to a syncytiotrophoblast layer. Media containing serum‐complexed [14C]‐α tocopherol was delivered to the apical side of the cells for 48 hrs and the replaced with serum free media. Cells that express TTP displayed significant (ca. 2‐fold) increase in the extent of tocopherol secretion by the monolayer. These findings show that placental TTP is necessary for trans‐placental transport of vitamin E. The functional consequences of heritable mutations in the TTPA gene on trans‐placental vitamin E transport are being addressed in ongoing experiments.