How does retinoic acid cause teratogenesis?
There are thirty-eight human Hox genes. In embryos exposed to excess retinoic acid, the Hox gene malfunction, which thereby disrupts the genetic control of body shape (axial patterning) in a developing embryo.
Is retinoic acid teratogenic?
Retinoic acid, an active metabolite of vitamin A, plays essential signaling roles in mammalian embryogenesis. Nevertheless, it has long been recognized that overexposure to vitamin A or retinoic acid causes widespread teratogenesis in rodents as well as humans.
How is retinal converted to retinoic acid?
Retinal can also be oxidized to retinoic acid (RA): retinal + NAD+ + H2O → retinoic acid + NADH + H+ (catalyzed by RALDH) retinal + O2 + H2O → retinoic acid + H2O2 (catalyzed by retinal oxidase), catalyzed by retinal dehydrogenases also known as retinaldehyde dehydrogenases (RALDHs) as well as retinal oxidases.
What enzyme converts retinol to retinoic acid?
retinol dehydrogenase
18.3. Retinoic acid (RA) is derived from vitamin A by retinol dehydrogenase (Rdh) in the oxidation of retinol to retinaldehyde, and then by retinaldehyde dehydrogenases (Raldh) for oxidation of retinaldehyde to RA (Duester, 2008). The LGE is a localized source of RA production (Toresson et al., 1999).
What is teratogenic action?
Teratogenic drugs: A teratogen is an agent that can disturb the development of the embryo or fetus. Teratogens halt the pregnancy or produce a congenital malformation (a birth defect). Classes of teratogens include radiation, maternal infections, chemicals, and drugs.
How does retinol affect breastfeeding?
Why You Should Not Use Retinol While Breastfeeding “Systemic retinoids, like isotretinoin, can cause birth defects, and therefore we do not recommend using retinoids of any kind during pregnancy or breastfeeding, despite minimal systemic absorption,” Dr. King says.
What is a teratogenic effect?
Teratogens are drugs, chemicals, or even infections that can cause abnormal fetal development. There are billions of potential teratogens, but only a few agents are proven to have teratogenic effects. These effects can result in a baby being born with a birth defect.
How do you synthesize retinol?
Retinol is synthesized from the breakdown of β-carotene. First, the β-carotene 15-15′-monooxygenase cleaves β-carotene at the central double bond, creating an epoxide. This epoxide is then attacked by water creating two hydroxyl groups in the center of the structure.
How do you absorb retinol?
Retinol is only absorbed efficiently when it is incorporated into mixed micelles along with lipase-digested fat (fatty acids and monoglycerides), bile acids, and phospholipids (Harrison and Hussain, 2001).
What causes teratogenesis?
Causes of teratogenesis can broadly be classified as: Toxic substances, such as, for humans, drugs in pregnancy and environmental toxins in pregnancy. Potassium iodide is a possible teratogen. Potassium iodide in its raw form is a mild irritant and should be handled with gloves.
What is the critical period during embryogenesis for teratogenesis?
The critical period of exposure appears to be 24 to 36 days after fertilization. Infectious agents can also cause a variety of birth defects and mental retardation when they cross the placenta and enter the fetal blood stream.
Where does the Teratology of retinoids come from?
Teratology of Retinoids. Abstract. Either an excess or a deficiency of vitamin A and related compounds (retinoids) causes abnormal morphological development (teratogenesis). Potential retinoid sources come from dietary intake, nutritional supplements, and some therapeutic drugs.
How does teratogenic retinoic acid affect the embryo?
Teratogenic retinoic acid may disrupt these levels. These disruptions can then lead to developmental defects, particularly in the embryonic spinal cord, central nervous system, and spinal cord, where retinoic acid synthesis and catabolic enzymes are located.
How does the body convert retinoic acid to retinaldehyde?
Cells that require retinoic acid take up the retinol and convert it to retinoic acid, its metabolite, through two enzymes: retinol dehydrogenases (ROLDH) and retinal dehydrogenases (RALDH). The first enzyme, ROLDH, converts retinol to retinaldehyde. The second enzyme, RALDH, converts retinaldehyde into retinoic acid.
How are teratogenic mechanisms associated with medical drugs?
We identified six teratogenic mechanisms associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption and specific receptor- or enzyme-mediated teratogenesis. Many medications classified as class X are associated with at least one of these mechanisms.