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Mechanistic TOR is therefore critical for the growth of most fetal organs, and global mTOR deletion is embryonic lethal. This review discusses emerging evidence suggesting that mTOR signaling also has a role as a critical hub in the overall homeostatic control of fetal growth, adjusting the fetal growth trajectory according to the ability of the maternal supply line to support fetal growth. In the fetus, liver mTOR governs the secretion and phosphorylation of insulin-like growth factor binding protein 1 (IGFBP-1) thereby controlling the bioavailability of insulin-like growth factors (IGF-I and IGF-II), which function as important growth hormones during fetal life. In the placenta, mTOR responds to a large number of growth-related signals, including amino acids, glucose, oxygen, folate, and growth factors, to regulate trophoblast mitochondrial respiration, nutrient transport, and protein synthesis, thereby influencing fetal growth. In the maternal compartment, mTOR is an integral part of a decidual nutrient sensor which links oxygen and nutrient availability to the phosphorylation of IGFBP-1 with preferential effects on the bioavailability of IGF-I in the maternal\u2013fetal interface and in the maternal circulation. These new roles of mTOR signaling in the regulation fetal growth will help us better understand the molecular underpinnings of abnormal fetal growth, such as intrauterine growth restriction and fetal overgrowth, and may represent novel avenues for diagnostics and intervention in important pregnancy complications.<\/jats:p>","DOI":"10.1093\/biolre\/ioy249","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T17:24:10Z","timestamp":1542821050000},"page":"872-884","source":"Crossref","is-referenced-by-count":64,"title":["Novel roles of mechanistic target of rapamycin signaling in regulating fetal growth\u2020"],"prefix":"10.1093","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9197-0341","authenticated-orcid":false,"given":"Madhulika B","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Western Ontario, London, Ontario, Canada"},{"name":"Department of Biochemistry, University of Western Ontario, London, Ontario, Canada"},{"name":"Children's Health Research Institute, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Jansson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado | Anschutz Medical Campus, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,11,21]]},"reference":[{"issue":"Suppl 3","key":"2019081904551121100_bib1","first-page":"332","article-title":"Intrauterine growth retardation (IUGR): epidemiology and etiology","volume":"6","author":"Romo","year":"2009","journal-title":"Pediatr Endocrinol Rev"},{"issue":"3","key":"2019081904551121100_bib2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1097\/AOG.0000000000002199","article-title":"Neonatal morbidity of small- and large-for-gestational-age neonates born at term in 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