The researchers studied the role of LRAT, a protein that facilitates the formation of vitamin A stores in the body, during embryonic development. In particular, they showed how LRAT protects developing tissues from potentially toxic levels of vitamin A that have been ingested by the mother. Although this function of LRAT had previously been hypothesized in adults, this is the first time that its role has been demonstrated during embryonic development.
The developing mammalian embryo is entirely dependent on the maternal circulation for its supply of retinoids, the vitamin A metabolites produced in the body. These are essential nutrients and they control the formation of the embryo’s heart, central nervous system, eyes and other important organs and tissues. Malformations of the developing embryo can occur when too little, or too much, vitamin A is consumed by the mother.
“We were looking for the mechanisms that allow the fetus to maintain adequate amount of retinoids, whether the mother has over- or under-consumed vitamin A,” said Dr. Loredana Quadro, an assistant professor in the Department of Food Science and member of the Center for Lipid Research at the Rutgers School of Environmental and Biological Sciences. “We also looked at the effects of different levels of vitamin A being transferred from the mother to the fetus.”
When vitamin A is ingested, it is converted into retinyl ester (RE) in the intestine from where it is secreted in the bloodstream packaged with other dietary lipids into lipoprotein particles called chylomicrons. The majority of dietary RE reaches the liver, the main body storage site of vitamin A. Under insufficient dietary vitamin A intake, the liver transforms RE into retinol (ROH), which is then secreted into the bloodstream bound to retinol-binding protein (RBP), its sole specific serum carrier, to be delivered to the target tissues. Upon intake through a specific membrane receptor named Stra6, ROH is ultimately converted to retinoic acid (RA), which is the active form of vitamin A. If tissue RA is in excess, it is transformed into inactive forms, such as 4-hydroxy retinoic acid or 4-oxo retinoic acid (OXO-RA) by the action of a specific enzyme named Cyp26A1.
“When we think about vitamin A, we think about one compound,” said Quadro. “But in reality, the term vitamin A comprises a family of different compounds. Each one has a slightly different action, and plays a different role.”
The Rutgers researchers took a closer look at how ROH is metabolized into RE and RA to maintain an optimal balance of retinoids during the formation of the embryo. Mutant mice lacking both RBP and LRAT were generated to perform this study, so as to interfere with the two main pathways of maternal vitamin A delivery to the fetus (ROH-RBP from the liver stores and RE of dietary origin).
“We hypothesized that the lack of ROH-RBP and LRAT would make the embryo more vulnerable to changes in maternal dietary vitamin A intake,” said Quadro “and our data proved this to be correct. Indeed, a severe embryonic vitamin A deficiency is readily attainable when the mothers are deprived of dietary vitamin A during pregnancy. Therefore, this strain turned out to be a very good model to study how embryonic development is affected by fluctuations in the amount of retinoids present in the maternal diet and hence in the maternal circulation”.
The researchers identified LRAT, Cyp26A1 and Stra6 as the three key molecular players that act in coordination to protect the developing tissues from potentially detrimental levels of vitamin A ingested by the mother. Understanding vitamin A metabolism in the developing fetus could have broad implications. Consumption of large doses of dietary supplements and vitamins, including vitamin A, has become a very common practice in recent years, generating the necessity to investigate the effects of high doses of vitamin A intake at different stages of the lifecycle, including pregnancy and development. These studies expand our knowledge of maternal-fetal nutrition and dietary contribution to embryonic development and may ultimately provide new insight into appropriate dietary practices during pregnancy.
This research was lead by Quadro and carried out primarily by her lab members, Youn-Kyung Kim, a graduate assistant, and Dr. Lesley Wassef, a post-doctoral associate. Others contributing to the study were Leora Hamberger, a former research assistant in Quadro’s laboratory, Dr. William Blaner and Roseann Piantedosi from Columbia University and Dr. Krzysztof Palczewski from Case Western Reserve.
The paper was previously published on the Journal of Biological Chemistry’s web site on December 19, 2007.Contact: Michele Hujber
Michele Hujber | EurekAlert!
Nanoparticles as a Solution against Antibiotic Resistance?
15.12.2017 | Friedrich-Schiller-Universität Jena
Plasmonic biosensors enable development of new easy-to-use health tests
14.12.2017 | Aalto University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences