Editing Choline (section)

==Perinatal development==
{{more citations needed section|date=December 2016}}

Both pregnancy and lactation increase demand for choline dramatically. This demand may be met by upregulation of [[Phosphatidyl ethanolamine methyltransferase|PEMT]] via increasing [[estrogen]] levels to produce more choline ''de novo'', but even with increased PEMT activity, the demand for choline is still so high that bodily stores are generally depleted. This is exemplified by the observation that ''Pemt −/−'' mice (mice lacking functional PEMT) will abort at 9–10 days unless fed supplemental choline.<ref name="Zeisel, SH. Choline 2006">{{cite journal | vauthors = Zeisel SH | title = Choline: critical role during fetal development and dietary requirements in adults | journal = Annual Review of Nutrition | volume = 26 | pages = 229–50 | year = 2006 | pmid = 16848706 | pmc = 2441939 | doi = 10.1146/annurev.nutr.26.061505.111156 }}</ref>

While maternal stores of choline are depleted during pregnancy and lactation, the placenta accumulates choline by pumping choline against the concentration gradient into the tissue, where it is then stored in various forms, mostly as acetylcholine. Choline concentrations in [[amniotic fluid]] can be ten times higher than in maternal blood.<ref name="Zeisel, SH. Choline 2006"/>

===Functions in the fetus===
Choline is in high demand during pregnancy as a substrate for building [[cellular membrane]]s (rapid fetal and mother tissue expansion), increased need for one-carbon [[Moiety (chemistry)|moieties]] (a substrate for methylation of DNA and other functions), raising choline stores in fetal and placental tissues, and for increased production of lipoproteins (proteins containing "fat" portions).<ref>{{cite book | title = Institute of Medicine, Food and Nutrition Board. Dietary reference intakes for Thiamine, Riboflavin, Niacin, Vitamin B<sub>6</sub>, Folate, Vitamin B<sub>12</sub>, Pantothenic Acid, Biotin and Choline. | location = Washington, DC | publisher = National Academies Press | date = 1998 }}</ref><ref>{{cite book | vauthors = Allen LH | chapter = Pregnancy and lactation | veditors = Bowman BA, Russle RM | title = Present Knowledge in Nutrition | location = Washington DC | publisher = ILSI Press | date = 2006 | pages = 529–543 }}</ref><ref>{{cite journal | vauthors = King JC | title = Physiology of pregnancy and nutrient metabolism | journal = The American Journal of Clinical Nutrition | volume = 71 | issue = 5 Suppl | pages = 1218S–25S | date = May 2000 | pmid = 10799394 | doi = 10.1093/ajcn/71.5.1218s | doi-access = free }}</ref> In particular, there is interest in the impact of choline consumption on the brain. This stems from choline's use as a material for making cellular membranes (particularly in making phosphatidylcholine). Human brain growth is most rapid during the [[third trimester]] of pregnancy and continues to be rapid to approximately five years of age.<ref>{{cite journal | vauthors = Morgane PJ, Mokler DJ, Galler JR | title = Effects of prenatal protein malnutrition on the hippocampal formation | journal = Neuroscience and Biobehavioral Reviews | volume = 26 | issue = 4 | pages = 471–83 | date = June 2002 | pmid = 12204193 | doi = 10.1016/s0149-7634(02)00012-x | s2cid = 7051841 }}</ref> During this time, the demand is high for sphingomyelin, which is made from phosphatidylcholine (and thus from choline), because this material is used to [[Myelinated nerve fibers|myelinate]] (insulate) [[nerve fiber]]s.<ref>{{cite journal | vauthors = Oshida K, Shimizu T, Takase M, Tamura Y, Shimizu T, Yamashiro Y | title = Effects of dietary sphingomyelin on central nervous system myelination in developing rats | journal = Pediatric Research | volume = 53 | issue = 4 | pages = 589–93 | date = April 2003 | pmid = 12612207 | doi = 10.1203/01.pdr.0000054654.73826.ac | doi-access = free }}</ref> Choline is also in demand for the production of the neurotransmitter acetylcholine, which can influence the structure and organization of brain regions, [[neurogenesis]], myelination, and [[synapse]] formation. Acetylcholine is even present in the placenta and may help control [[cell proliferation]] and [[Cell differentiation|differentiation]] (increases in cell number and changes of multiuse cells into dedicated cellular functions) and [[parturition]].<ref>{{cite journal | vauthors = Sastry BV | title = Human placental cholinergic system | journal = Biochemical Pharmacology | volume = 53 | issue = 11 | pages = 1577–86 | date = June 1997 | pmid = 9264309 | doi = 10.1016/s0006-2952(97)00017-8 }}</ref><ref>{{cite journal | vauthors = Sastry BV, Sadavongvivad C | title = Cholinergic systems in non-nervous tissues | journal = Pharmacological Reviews | volume = 30 | issue = 1 | pages = 65–132 | date = March 1978 | pmid = 377313 }}</ref>

Choline uptake into the brain is controlled by a low-affinity transporter located at the blood–brain barrier.<ref>{{cite journal | vauthors = Lockman PR, Allen DD | title = The transport of choline | journal = Drug Development and Industrial Pharmacy | volume = 28 | issue = 7 | pages = 749–71 | date = August 2002 | pmid = 12236062 | doi = 10.1081/DDC-120005622 | s2cid = 34402785 }}</ref> Transport occurs when arterial blood plasma choline concentrations increase above 14&nbsp;μmol/L, which can occur during a spike in choline concentration after consuming choline-rich foods. Neurons, conversely, acquire choline by both high- and low-affinity transporters. Choline is stored as membrane-bound phosphatidylcholine, which can then be used for acetylcholine neurotransmitter synthesis later. Acetylcholine is formed as needed, travels across the synapse, and transmits the signal to the following neuron. Afterwards, [[acetylcholinesterase]] degrades it, and the free choline is taken up by a high-affinity transporter into the neuron again.<ref>{{cite journal | vauthors = Caudill MA | title = Pre- and postnatal health: evidence of increased choline needs | journal = Journal of the American Dietetic Association | volume = 110 | issue = 8 | pages = 1198–206 | date = August 2010 | pmid = 20656095 | doi = 10.1016/j.jada.2010.05.009 }}</ref>