{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T17:00:16Z","timestamp":1776963616119,"version":"3.51.4"},"reference-count":45,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:p> Enhancing placental insulin-like growth factor (IGF) availability appears to be an attractive strategy for improving outcomes in fetal growth restriction (FGR). Our approach was the novel use of [Leu<jats:sup>27<\/jats:sup>]IGF-II, a human IGF-II analog that binds the IGF-II clearance receptor IGF-IIR in fetal growth-restricted (FGR) mice. We hypothesized that the impact of [Leu<jats:sup>27<\/jats:sup>]IGF-II infusion in C57BL\/6J (wild-type) and endothelial nitric oxide synthase knockout (eNOS<jats:sup>\u2212\/\u2212<\/jats:sup>; FGR) mice would be to enhance fetal growth and investigated this from mid- to late gestation; 1 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> [Leu<jats:sup>27<\/jats:sup>]IGF-II was delivered via a subcutaneous miniosmotic pump from E12.5 to E18.5. Fetal and placental weights recorded at E18.5 were used to generate frequency distribution curves; fetuses &lt;5th centile were deemed growth restricted. Placentas were harvested for immunohistochemical analysis of the IGF system, and maternal serum was collected for measurement of exogenously administered IGF-II. In WT pregnancies, [Leu<jats:sup>27<\/jats:sup>]IGF-II treatment halved the number of FGR fetuses, reduced fetal( P = 0.028) and placental weight variations ( P = 0.0032), and increased the numbers of pups close to the mean fetal weight (131 vs. 112 pups within 1 SD). Mixed-model analysis confirmed litter size to be negatively correlated with fetal and placental weight and showed that [Leu<jats:sup>27<\/jats:sup>]IGF-II preferentially improved fetal weight in the largest litters, as defined by number. Unidirectional <jats:sup>14C<\/jats:sup>MeAIB transfer per gram placenta (System A amino acid transporter activity) was inversely correlated with fetal weight in [Leu<jats:sup>27<\/jats:sup>]IGF-II-treated WT animals ( P &lt; 0.01). In eNOS<jats:sup>\u2212\/\u2212<\/jats:sup> mice, [Leu<jats:sup>27<\/jats:sup>]IGF-II reduced the number of FGR fetuses(1 vs. 5 in the untreated group). The observed reduction in FGR pup numbers in both C57 and eNOS<jats:sup>\u2212\/\u2212<\/jats:sup> litters suggests the use of this analog as a means of standardizing and rescuing fetal growth, preferentially in the smallest offspring. <\/jats:p>","DOI":"10.1152\/ajpendo.00379.2015","type":"journal-article","created":{"date-parts":[[2015,11,4]],"date-time":"2015-11-04T03:44:18Z","timestamp":1446608658000},"page":"E24-E31","source":"Crossref","is-referenced-by-count":19,"title":["The impact of a human IGF-II analog ([Leu<sup>27<\/sup>]IGF-II) on fetal growth in a mouse model of fetal growth restriction"],"prefix":"10.1152","volume":"310","author":[{"given":"Jayne C.","family":"Charnock","sequence":"first","affiliation":[{"name":"Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester, United Kingdom; and"},{"name":"Maternal and Fetal Health Research Centre, St. Mary's Hospital, Central Manchester Universities National Health 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