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Choline Distribution and Metabolism in Pregnant Rats and Fetuses are Influenced by the Choline Content of the Maternal Diet^1,2,3,

Sanford C. Garner^*, Mei-Heng Mar and Steven H. Zeisel^,4

^* Department of Surgery, Duke University, Duke University Medical Center, Durham, NC 27710 Department of Nutrition, University of North Carolina at Chapel Hill, School of Public Health, School of Medicine, CB#7400, Chapel Hill, NC 27599-7400

Choline supplementation of pregnant rats between d 12 and 17 of pregnancy permanently enhances the spatial memory of offspring; however, the mechanism is unknown. We examined the effect of choline supplementation on metabolism of orally ingested choline by nonmated rats and pregnant rats and their fetuses. We studied the metabolism of an acute oral dose of ¹⁴C-choline chloride in pregnant and nonmated rats with and without choline supplementation (25 mmol/L choline chloride in water) on d 12–17 of pregnancy. During the first 2 h after oral dosing, plasma radiolabeled choline was detectable, whereas plasma choline metabolites contributed little to total radioactivity at any time. The pattern of accumulation of label in placentas was similar in all groups. Fetal tissues (i.e., brain, liver and carcass remnant) contained primarily ¹⁴C-phosphatidylcholine and ¹⁴C-phosphorylcholine. Also, we examined the fetal tissue distribution of isotopically labeled (deuterated) choline derived from the diet and from the dietary choline supplement. The distribution patterns for radiolabeled choline metabolites in fetuses of supplemented dams accumulated significantly (P < 0.01) more of their total choline and its metabolites than fetuses of control dams during d 12–17 of gestation (50 vs. 20%). In fetuses from supplemented dams, betaine concentrations were greater than in fetuses from control dams in all organs assayed (by 36–57%). Phosphorylcholine concentrations in brain of fetuses from supplemented dams were also greater. These experiments identify potential metabolites of choline that might mediate the observed effects on brain development in the rats.

KEY WORDS: • choline • pregnancy • betaine • phosphorylcholine • rats

¹ This work was supported by Grant AG09525 from the National Institutes of Health, a grant from Central Soya Company and a grant from the University of North Carolina Institute of Nutrition.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ Some of the described data were previously reported in abstract form (Garner, S. C., Mar, M.-H., Zeisel, S. H. (1992) Choline metabolism by fetal rats. FASEB J. 6: 1941) at the Federation of American Societies for Experimental Biology, April 1992, Anaheim, CA.

⁴ To whom correspondence should be addressed.

Manuscript received 20 March 1995. Revision accepted 24 July 1995.

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