{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T03:25:54Z","timestamp":1771298754893,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T00:00:00Z","timestamp":1585872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>A relatively large branched-chain amino acid (BCAA) supplement, consumed for more than 10 days, appears to be especially effective at alleviating muscle damage and soreness during intense human training. However, perturbations in amino acid and protein consumption could have unwanted transgenerational effects on male and female reproduction. This paper hypothesizes that isoleucine consumption by female mice from days 2 to 10 of pregnancy will alter fetal and placental growth later in gestation. Mice that had received 118 mM isoleucine in their drinking water delivered pups on day 19 of pregnancy that were 9% larger than normal, whereas the reverse was true for pups born on day 20. Moreover, the inverse correlation between birth weight and litter size was lost in mice that previously consumed excess isoleucine. Similarly, the normal correlations between fetal and placental weights were lost by day 18 of pregnancy in mice that had consumed excess isoleucine. Mice that consumed excess isoleucine had placentas smaller than, and fetuses larger than normal on day 18 of pregnancy, but the reverse was true on day 15. Other unintended and unexpected effects of BCAA consumption should be studied more thoroughly due to the increasing use of BCAAs to alleviate muscle damage and soreness in athletes.<\/jats:p>","DOI":"10.3390\/ijerph17072445","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T06:10:28Z","timestamp":1586153428000},"page":"2445","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Consumption of a Branched-Chain Amino Acid (BCAA) during Days 2\u201310 of Pregnancy Causes Abnormal Fetal and Placental Growth: Implications for BCAA Supplementation in Humans"],"prefix":"10.3390","volume":"17","author":[{"given":"Chiu Yuen","family":"To","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Neurosurgery, St Francis Hospital, Memphis, TN 38119, USA"},{"name":"Department of Biochemistry, Midwestern University, Downers Grove, IL 60515, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muriel","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Midwestern University, Downers Grove, IL 60515, USA"},{"name":"Department of Surgery, Division of Podiatric Medicine and Surgery, Carle Richland Memorial Hospital, Olney, IL 62450, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2223-0419","authenticated-orcid":false,"given":"Lon J.","family":"Van Winkle","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Midwestern University, Downers Grove, IL 60515, USA"},{"name":"Department of Medical Humanities, Rocky Vista University 8401 S. Chambers Road, Parker, CO 80134, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,3]]},"reference":[{"key":"ref_1","first-page":"424","article-title":"Branched-chain amino acid supplementation attenuates muscle soreness, muscle damage and inflammation during an intensive training program","volume":"49","author":"Matsumoto","year":"2009","journal-title":"J. Sports Med. Phys. Fit."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1249\/MSS.0b013e3181c1b798","article-title":"Branched-chain amino acid ingestion can ameliorate soreness from eccentric exercise","volume":"42","author":"Jackman","year":"2010","journal-title":"Med. Sci. Sport Exerc."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Four\u00e9, A., and Bendahan, D. (2017). Is branched-chain amino acids supplementation an efficient nutritional strategy to alleviate skeletal muscle damage? A systematic review. Nutrients, 9.","DOI":"10.3390\/nu9101047"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s00421-008-0832-5","article-title":"Effects of branched-chain amino acids supplementation on physiological and psychological performance during an offshore sailing race","volume":"104","author":"Portier","year":"2008","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1550-2783-9-20","article-title":"Exercise-induced muscle damage is reduced in resistance-trained males by branched chain amino acids: A randomized, double-blind, placebo controlled study","volume":"9","author":"Howatson","year":"2012","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3945\/jn.110.128520","article-title":"Higher branched-chain amino acid intake is associated with a lower prevalence of being overweight or obese in middle-aged East Asian and Western adults","volume":"141","author":"Qin","year":"2010","journal-title":"J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9573","DOI":"10.3390\/nu7115486","article-title":"The ratio of dietary branched-chain amino acids is associated with a lower prevalence of obesity in young northern Chinese adults: An internet-based cross-sectional study","volume":"7","author":"Li","year":"2015","journal-title":"Nutrients"},{"key":"ref_8","first-page":"43","article-title":"Meta-analysis of branched chain amino acid-enriched nutrition to improve hepatic function in patients undergoing hepatic operation","volume":"22","author":"Shu","year":"2014","journal-title":"Chin. J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1016\/S0140-6736(18)30312-X","article-title":"Origins of lifetime health around the time of conception: Causes and consequences","volume":"391","author":"Fleming","year":"2018","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1515\/bmc-2018-0017","article-title":"Can uterine secretion of modified histones alter blastocyst implantation, embryo nutrition, and transgenerational phenotype?","volume":"9","author":"Ryznar","year":"2018","journal-title":"Biomol. Concepts"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"300","DOI":"10.3389\/fcell.2019.00300","article-title":"One-carbon metabolism regulates embryonic stem cell fate through epigenetic DNA and histone modifications: Implications for transgenerational metabolic disorders in adults","volume":"7","author":"Ryznar","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1017\/S0007114599000446","article-title":"The effects of maternal protein restriction on the growth of the rat fetus and its amino acid supply","volume":"81","author":"Rees","year":"1999","journal-title":"Br. J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.2337\/diacare.26.9.2512","article-title":"Prenatal growth, BMI, and risk of type 2 diabetes by early midlife","volume":"26","author":"Power","year":"2003","journal-title":"Diabets Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1055\/s-2007-964940","article-title":"Branched-chain amino acids and arginine supplementation attenuates skeletal muscle proteolysis induced by moderate exercise in young individuals","volume":"28","author":"Matsumoto","year":"2007","journal-title":"Int. J. Sports Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/humupd\/dmi044","article-title":"System B0,+ amino acid transport regulates the penetration stage of blastocyst implantation with possible long-term developmental consequences through adulthood","volume":"12","author":"Tesch","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/0005-2736(90)90318-I","article-title":"Transport of benzenoid amino acids by system T and four broad scope systems in preimplantation mouse conceptuses","volume":"1027","author":"Mann","year":"1990","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1095\/biolreprod52.1.96","article-title":"Differences in amino acid content of preimplantation mouse embryos that develop in vitro versus in vivo: In vitro effects of five amino acids that are abundant in oviductal secretions","volume":"52","author":"Dickinson","year":"1995","journal-title":"Biol. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/S1472-6483(10)62075-5","article-title":"On a fallacious invocation of the Barker hypothesis of anomalies in newborn rats due to mothers\u2019 food restriction in preimplantation phases","volume":"7","author":"Walters","year":"2003","journal-title":"Reprod. Biomed. Online"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/S1472-6483(10)61105-4","article-title":"Support for Barker hypothesis upheld in rat model of maternal undernutrition during the preimplantation period: Application of integrated \u2018random effects\u2019 statistical model","volume":"8","author":"Kwong","year":"2004","journal-title":"Reprod. Biomed. Online"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S1472-6483(10)62121-9","article-title":"Further thoughts regarding evidence offered in support of the \u2018Barker hypothesis\u2019","volume":"9","author":"Walters","year":"2004","journal-title":"Reprod. Biomed. Online"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1023\/B:AHSE.0000038173.00909.f6","article-title":"A visitor\u2019s guide to effect sizes\u2013statistical significance versus practical (clinical) importance of research findings","volume":"9","author":"Hojat","year":"2004","journal-title":"Adv. Health Sci. Educ."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10064","DOI":"10.1073\/pnas.1806333115","article-title":"Paternal diet programs offspring health through sperm-and seminal plasma-specific pathways in mice","volume":"115","author":"Watkins","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1210\/en.2010-1153","article-title":"Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters","volume":"152","author":"Rosario","year":"2011","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1113\/jphysiol.2012.238014","article-title":"Mammalian target of rapamycin signaling modulates amino acid uptake by regulating transporter cell surface abundance in primary human trophoblast cells","volume":"591","author":"Rosario","year":"2013","journal-title":"J. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1093\/jn\/130.7.1821","article-title":"Maternal protein deficiency causes hypermethylation of DNA in the livers of rat fetuses","volume":"130","author":"Rees","year":"2000","journal-title":"J. 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