Alpha-tocopherol transfer protein (alpha-TTP) was first described to play a major role in maintaining alpha-tocopherol levels in plasma, while alpha-tocopherol was primarily reported to be a factor relevant for reproduction. Expression of alpha-TTP is not only seen in the liver, from where it was first isolated, but also in mouse uterus, depending on its state of pregnancy, stressing the importance of alpha-TTP for embryogenesis and fetal development. The cellular localization of alpha-TTP in mouse uterus is reported here. By immunohistochemistry, alpha-TTP could be localized in the secretory columnar epithelial cells of the pregnant uterus on Days 4.5 and 6.5 postcoitum as well as in the glandular epithelial cells and the inner decidual reaction zone surrounding the implantation site. On Days 8.5 and 10.5 postcoitum (midterm of mouse pregnancy), alpha-TTP could still be detected in the uterine secretory columnar epithelial cells, while in alpha-TTP knockout mice, no immunostaining was visible. It is suggested that alpha-TTP plays a major role in supplying the placenta and consecutively the fetus with alpha-tocopherol throughout pregnancy. We conclude that alpha-tocopherol plays a role in the process of implantation and that alpha-TTP may be necessary for adequate alpha-tocopherol status of the fetus.
"Fetal resorption and placental failure have been noted in TTP knockout mice , , which are similar to outcomes observed upon diet-induced vitamin E deficiency , , . The TTP protein is expressed in the placental and uterine cells of mice and humans –, , and is thought to play an important role in supplying maternal α-tocopherol to the developing fetus to protect against oxidative stress . The mammalian studies provide insight into the requirement of TTP for implantation and placental formation, both of which are linked to maternal transfer and need, but fail to determine the TTP requirement of the developing fetus. "
[Show abstract][Hide abstract] ABSTRACT: The hepatic α-tocopherol transfer protein (TTP) is required for optimal α-tocopherol bioavailability in humans; mutations in the human TTPA gene result in the heritable disorder ataxia with vitamin E deficiency (AVED, OMIM #277460). TTP is also expressed in mammalian uterine and placental cells and in the human embryonic yolk-sac, underscoring TTP's significance during fetal development. TTP and vitamin E are essential for productive pregnancy in rodents, but their precise physiological role in embryogenesis is unknown. We hypothesize that TTP is required to regulate delivery of α-tocopherol to critical target sites in the developing embryo. We tested to find if TTP is essential for proper vertebrate development, utilizing the zebrafish as a non-placental model. We verify that TTP is expressed in the adult zebrafish and its amino acid sequence is homologous to the human ortholog. We show that embryonic transcription of TTP mRNA increases >7-fold during the first 24 hours following fertilization. In situ hybridization demonstrates that Ttpa transcripts are localized in the developing brain, eyes and tail bud at 1-day post fertilization. Inhibiting TTP expression using oligonucleotide morpholinos results in severe malformations of the head and eyes in nearly all morpholino-injected embryos (88% compared with 5.6% in those injected with control morpholinos or 1.7% in non-injected embryos). We conclude that TTP is essential for early development of the vertebrate central nervous system.
PLoS ONE 10/2012; 7(10):e47402. DOI:10.1371/journal.pone.0047402 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: α-Tocopherol transfer protein (α-TTP), a 30 kDa cytosolic protein first described to be present in the liver and important for α-tocopherol trafficking, plays a major role in maintaining α-tocopherol levels in plasma, while α-tocopherol is known as the major lipid-soluble antioxidant. Expression of α-TTP has not only been described in animal model liver, but also in diverse other tissues such as rat brain or pregnant mouse uterus, the latter finding stressing the importance of α-TTP for embryogenesis and foetal development. In this study, we report the identification of α-TTP in human liver by anti-human α-TTP monoclonal antibodies made in rat and the cellular localization of α-TTP in term human placenta. By immunohistochemistry, intense staining of α-TTP was seen in syncytiotrophoblast as well as in villous and invading extravillous cytotrophoblast, while basal decidual cells showed slighter, but present staining of α-TTP. Foetal vessel endothelium remained unstained. It is therefore suggested that α-TTP may play a major role in supplying α-tocopherol to the foetus prior to delivery and is likely involved in maintaining adequate α-tocopherol levels in the foetus.
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