Editing Vitamin A (section)

===Embryology===
In vertebrates and invertebrate chordates, RA has a pivotal role during development. Altering levels of endogenous RA signaling during early embryology, either too low or too high, leads to birth defects,<ref>{{cite journal | vauthors = Metzler MA, Sandell LL | title = Enzymatic Metabolism of Vitamin A in Developing Vertebrate Embryos | journal = Nutrients | volume = 8 | issue = 12 | page = 812 | date = December 2016 | pmid = 27983671 | pmc = 5188467 | doi = 10.3390/nu8120812 | doi-access = free | title-link = doi }}</ref><ref name=Marletaz2006>{{cite journal | vauthors = Marlétaz F, Holland LZ, Laudet V, Schubert M | title = Retinoic acid signaling and the evolution of chordates | journal = International Journal of Biological Sciences | volume = 2 | issue = 2 | pages = 38–47 | date = 2006 | pmid = 16733532 | pmc = 1458431 | doi = 10.7150/ijbs.2.38 }}</ref> including congenital vascular and cardiovascular defects.<ref>{{cite journal | vauthors = Pawlikowski B, Wragge J, Siegenthaler JA | title = Retinoic acid signaling in vascular development | journal = Genesis | volume = 57 | issue = 7–8 | pages = e23287 | date = July 2019 | pmid = 30801891 | pmc = 6684837 | doi = 10.1002/dvg.23287 }}</ref><ref>{{cite journal | vauthors = Wang S, Moise AR | title = Recent insights on the role and regulation of retinoic acid signaling during epicardial development | journal = Genesis | volume = 57 | issue = 7–8 | pages = e23303 | date = July 2019 | pmid = 31066193 | pmc = 6682438 | doi = 10.1002/dvg.23303 }}</ref> Of note, fetal alcohol spectrum disorder encompasses congenital anomalies, including craniofacial, auditory, and ocular defects, neurobehavioral anomalies and mental disabilities caused by maternal consumption of alcohol during pregnancy. It is proposed that in the embryo there is competition between acetaldehyde, an ethanol metabolite, and retinaldehyde (retinal) for aldehyde dehydrogenase activity, resulting in a retinoic acid deficiency, and attributing the congenital birth defects to the loss of RA activated gene activation. In support of this theory, ethanol-induced developmental defects can be ameliorated by increasing the levels of retinol or retinal.<ref name="Shabtai2018A"/> As for the risks of too much RA during embryogenesis, the prescription drugs [[tretinoin]] (''all-trans''-retinoic acid) and [[isotretinoin]] (13-cis-retinoic acid), used orally or topically for acne treatment, are labeled with [[boxed warning]]s for pregnant women or women who may become pregnant, as they are known human teratogens.<ref name="Draghici2021">{{cite journal |vauthors=Draghici CC, Miulescu RG, Petca RC, Petca A, Dumitrașcu MC, Șandru F |date=May 2021 |title=Teratogenic effect of isotretinoin in both fertile females and males (Review) |journal=Experimental and Therapeutic Medicine |volume=21 |issue=5 |pages=534 |doi=10.3892/etm.2021.9966 |pmc=8014951 |pmid=33815607}}</ref><ref name="Tretinoin">{{cite web |date=1 July 2019 |title=Tretinoin topical Use During Pregnancy |url=https://www.drugs.com/pregnancy/tretinoin-topical.html |url-status=live |archive-url=https://web.archive.org/web/20201129110248/https://www.drugs.com/pregnancy/tretinoin-topical.html |archive-date=29 November 2020 |access-date=16 January 2020 |website=Drugs.com}}</ref>