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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Endocrinol+Metab
2016 ; 310
(1
): E24-31
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The impact of a human IGF-II analog ( Leu27 IGF-II) on fetal growth in a mouse
model of fetal growth restriction
#MMPMID26530156
Charnock JC
; Dilworth MR
; Aplin JD
; Sibley CP
; Westwood M
; Crocker IP
Am J Physiol Endocrinol Metab
2016[Jan]; 310
(1
): E24-31
PMID26530156
show ga
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(27)]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(27)]IGF-II infusion in C57BL/6J
(wild-type) and endothelial nitric oxide synthase knockout (eNOS(-/-); FGR) mice
would be to enhance fetal growth and investigated this from mid- to late
gestation; 1 mg·kg(-1)·day(-1) [Leu(27)]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 <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(27)]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(27)]IGF-II preferentially improved fetal weight in the largest
litters, as defined by number. Unidirectional (14C)MeAIB transfer per gram
placenta (System A amino acid transporter activity) was inversely correlated with
fetal weight in [Leu(27)]IGF-II-treated WT animals (P < 0.01). In eNOS(-/-) mice,
[Leu(27)]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(-/-)
litters suggests the use of this analog as a means of standardizing and rescuing
fetal growth, preferentially in the smallest offspring.