{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:16:47Z","timestamp":1760235407063,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD-066982"],"award-info":[{"award-number":["HD-066982"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dorothy Foehr Huck Endowment","award":["x"],"award-info":[{"award-number":["x"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Vitamin A (VA) plays critical roles in prenatal and postnatal development; however, limited information is available regarding maternal VA metabolism during pregnancy and lactation. Objectives: We investigated the impact of pregnancy and lactation on VA metabolism and kinetics in rats, hypothesizing that changes in physiological status would naturally perturb whole-body VA kinetics. Methods: Eight-week old female rats (n = 10) fed an AIN-93G diet received an oral tracer dose of 3H-labeled retinol to initiate the kinetic study. On d 21 after dosing, six female rats were mated. Serial blood samples were collected from each female rat at selected times after dose administration until d 14 of lactation. Model-based compartmental analysis was applied to the plasma tracer data to develop VA kinetic models. Results: Our compartmental model revealed that pregnancy resulted in a gradual increase in hepatic VA mobilization, presumably to support different stages of fetal development. Additionally, the model indicates that during lactation, VA derived from dietary intake was the primary source of VA delivered to the mammary gland for milk VA secretion. Conclusion: During pregnancy and lactation in rats with an adequate VA intake and previous VA storage, the internal redistribution of VA and increased uptake from diet supported the maintenance of VA homeostasis.<\/jats:p>","DOI":"10.3390\/nu13082853","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T09:58:06Z","timestamp":1629367086000},"page":"2853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pregnancy and Lactation Alter Vitamin A Metabolism and Kinetics in Rats under Vitamin A-Adequate Dietary Conditions"],"prefix":"10.3390","volume":"13","author":[{"given":"Yaqi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayasa","family":"Tajima","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7121-0206","authenticated-orcid":false,"given":"Floyd J.","family":"Mattie","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael H.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6180-9570","authenticated-orcid":false,"given":"A. Catharine","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA 16802, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/978-1-4899-2575-6_15","article-title":"The function of vitamin A in cellular growth and differentiation, and its roles during pregnancy and lactation","volume":"352","author":"Ross","year":"1994","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1001\/archopht.1946.00890200155008","article-title":"Congenital malformations induced in rats by maternal vitamin A deficiency; defects of the eye","volume":"35","author":"Warkany","year":"1946","journal-title":"Arch. Ophthal."},{"key":"ref_3","first-page":"376","article-title":"Anomalies of the genito-urinary tract induced by maternal vitamin A deficiency in fetal rats","volume":"97","author":"Wilson","year":"1947","journal-title":"Anat. Rec."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1126\/science.117.3046.535","article-title":"Excessive intake of vitamin A as a cause of congenital anomalies in the rat","volume":"117","author":"Cohlan","year":"1953","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/aja.1000920202","article-title":"An analysis of the syndrome of malformations induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation","volume":"92","author":"Wilson","year":"1953","journal-title":"Am. J. Anat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0015-6264(69)80324-X","article-title":"Variations in teratogenic response to hypervitaminosis A in three strains of the albino rat","volume":"7","author":"Nolen","year":"1969","journal-title":"Food Cosmet. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1093\/jn\/105.10.1299","article-title":"Vitam A deficiency and fetal growth and development in the rat","volume":"105","author":"Takahashi","year":"1975","journal-title":"J. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"351","DOI":"10.3109\/10408447909043651","article-title":"Hypervitaminosis A induced teratogenesis","volume":"6","author":"Geelen","year":"1979","journal-title":"CRC Crit. Rev. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1056\/NEJM199511233332101","article-title":"Teratogenicity of high vitamin A intake","volume":"333","author":"Rothman","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13459","DOI":"10.1073\/pnas.95.23.13459","article-title":"Defects in embryonic hindbrain development and fetal resorption resulting from vitamin A deficiency in the rat are prevented by feeding pharmacological levels of all-trans-retinoic acid","volume":"95","author":"White","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1017\/S0007114500001318","article-title":"Moderate maternal vitamin A deficiency affects perinatal organ growth and development in rats","volume":"84","author":"Antipatis","year":"2000","journal-title":"Br. J. Nutr."},{"key":"ref_12","first-page":"E263","article-title":"Vitamin A and retinol-binding protein metabolism during fetal development in the rat","volume":"233","author":"Takahashi","year":"1977","journal-title":"Am. J. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1093\/jn\/117.8.1410","article-title":"Vitamin A status needed to maintain vitamin A concentrations in nonhepatic tissues of the pregnant rat","volume":"117","author":"Wallingford","year":"1987","journal-title":"J. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1095\/biolreprod46.5.802","article-title":"Developmental changes in endogenous retinoids during pregnancy and embryogenesis in the mouse","volume":"46","author":"Satre","year":"1992","journal-title":"Biol. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/tera.1420500303","article-title":"Maternal toxicokinetics, metabolism, and embryo exposure following a teratogenic dosing regimen with 13-cis-retinoic acid (isotretinoin) in the cynomolgus monkey","volume":"50","author":"Hummler","year":"1994","journal-title":"Teratology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"209","DOI":"10.5487\/TR.2010.26.3.209","article-title":"Evaluation of embryotoxic potential of olaquindox and vitamin a in micromass culture and in rats","volume":"26","author":"Kang","year":"2010","journal-title":"Toxicol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1093\/jn\/111.7.1135","article-title":"Vitamin A turnover in rats as influenced by vitamin A status","volume":"111","author":"Lewis","year":"1981","journal-title":"J. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1194\/jlr.M600528-JLR200","article-title":"Model-based compartmental analysis indicates a reduced mobilization of hepatic vitamin A during inflammation in rats","volume":"48","author":"Gieng","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1194\/jlr.M045229","article-title":"Retinol kinetics in unsupplemented and vitamin A-retinoic acid supplemented neonatal rats: A preliminary model","volume":"55","author":"Tan","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3945\/jn.114.204065","article-title":"Vitamin A kinetics in neonatal rats vs. adult rats: Comparisons from model-based compartmental analysis","volume":"145","author":"Tan","year":"2015","journal-title":"J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.3945\/ajcn.116.149039","article-title":"Vitamin A supplementation redirects the flow of retinyl esters from peripheral to central organs of neonatal rats raised under vitamin A-marginal conditions","volume":"105","author":"Hodges","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1093\/jn\/nxz112","article-title":"Addition of vitamin A intake data during compartmental modeling of retinol kinetics in theoretical humans leads to accurate prediction of vitamin A total body stores and kinetic parameters in studies of reasonable duration","volume":"149","author":"Ford","year":"2019","journal-title":"J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1093\/jn\/nxz056","article-title":"Inclusion of vitamin A intake data provides improved compartmental model-derived estimates of vitamin A total body stores and disposal rate in older adults","volume":"149","author":"Green","year":"2019","journal-title":"J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/jn\/nxz225","article-title":"Use of model-based compartmental analysis and a super-child design to study whole-body retinol kinetics and vitamin A total body stores in children from 3 lower-income countries","volume":"150","author":"Ford","year":"2020","journal-title":"J. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1093\/jn\/nxaa098","article-title":"Dietary iron repletion stimulates hepatic mobilization of vitamin A in previously iron-deficient rats as determined by model-based compartmental analysis","volume":"150","author":"Li","year":"2020","journal-title":"J. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1093\/toxsci\/55.2.478","article-title":"Mobilization of vitamin A stores in rats after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin: A kinetic analysis","volume":"55","author":"Kelley","year":"2000","journal-title":"Toxicol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1194\/jlr.M600061-JLR200","article-title":"Vitamin A combined with retinoic acid increases retinol uptake and lung retinyl ester formation in a synergistic manner in neonatal rats","volume":"47","author":"Ross","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1093\/jn\/nxaa108","article-title":"Perturbed vitamin A status induced by iron deficiency is corrected by iron repletion in rats with pre-existing iron deficiency","volume":"150","author":"Li","year":"2020","journal-title":"J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0083-6729(06)75007-5","article-title":"Use of model-based compartmental analysis to study vitamin A kinetics and metabolism","volume":"75","author":"Cifelli","year":"2007","journal-title":"Vitam. Horm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1093\/jn\/131.4.1279","article-title":"Vitamin A intake affects the contribution of chylomicrons vs. retinol-binding protein to milk vitamin A in lactating rats","volume":"131","author":"Green","year":"2001","journal-title":"J. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7326","DOI":"10.1073\/pnas.79.23.7326","article-title":"In vivo uptake of chylomicron [3H]retinyl ester by rat liver: Evidence for retinol transfer from parenchymal to nonparenchymal cells","volume":"79","author":"Blomhoff","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"291S","DOI":"10.1093\/jn\/133.1.291S","article-title":"Retinoid production and catabolism: Role of diet in regulating retinol esterification and retinoic Acid oxidation","volume":"133","author":"Ross","year":"2003","journal-title":"J. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"269S","DOI":"10.1093\/jn\/134.1.269S","article-title":"Regulation of hepatic retinol metabolism: Perspectives from studies on vitamin A status","volume":"134","author":"Ross","year":"2004","journal-title":"J. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1093\/jn\/117.3.436","article-title":"Synthesis of retinol-binding protein and transthyretin in yolk sac and fetus in the rat","volume":"117","author":"Sklan","year":"1987","journal-title":"J. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0022-2275(20)38182-7","article-title":"Retinol esterification by mammary gland microsomes from the lactating rat","volume":"23","author":"Ross","year":"1982","journal-title":"J. Lipid Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1177\/153537020422900106","article-title":"Chylomicron margination, lipolysis, and vitamin a uptake in the lactating rat mammary gland: Implications for milk retinoid content","volume":"229","author":"Ross","year":"2004","journal-title":"Exp. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1093\/jn\/136.1.128","article-title":"Dietary vitamin A has both chronic and acute effects on vitamin A indices in lactating rats and their offspring","volume":"136","author":"Akohoue","year":"2006","journal-title":"J. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/8\/2853\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:47:30Z","timestamp":1760165250000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/8\/2853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,19]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["nu13082853"],"URL":"https:\/\/doi.org\/10.3390\/nu13082853","relation":{},"ISSN":["2072-6643"],"issn-type":[{"type":"electronic","value":"2072-6643"}],"subject":[],"published":{"date-parts":[[2021,8,19]]}}}