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Placenta. 2013 Dec;34(12):1150-8. doi: 10.1016/j.placenta.2013.09.011. Epub 2013 Sep 27.

Recapitulation of characteristics of human placental vascular insufficiency in a novel mouse model.

Author information

1
The Fetal Care Center of Cincinnati, Division of Pediatric General, Thoracic and Fetal Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Division of Maternal-Fetal Medicine, Cincinnati, OH, USA; University of Cincinnati College of Medicine, Cincinnati, OH, USA; Good Samaritan Hospital, Cincinnati, OH, USA. Electronic address: drmhabli@gmail.com.

Abstract

OBJECTIVE:

We tested the effects of selective reduction of placental blood flow by mesenteric uterine artery branch ligation (MUAL) resulting in fetal growth restriction (FGR).

METHODS:

Timed mated C57BL/6J Day(D) 18 dams were divided into two groups: MUAL (n = 18); and control-sham (n = 18). Pups were delivered on D20, cross-fostered to surrogate CD-1 mothers for 4 weeks, and followed for 8 weeks. Outcome data included birth and placental weight, postnatal growth, placental volume determined by stereology, quantification of placental insulin-like growth factors-1(IGF-1) and IGF-2 and IGF binding proteins(IGFBP 2 and 6) by ELISA and gene expression by qPCR and GeneChip microarray analysis.

RESULTS:

Compared with control, MUAL had an 11% reduction in mean birth weight (1.06 ± 0.13 g vs. 0.94 ± 0.13 g, p < 0.001) but no difference in placental weight. At 4 weeks of age, mean body weights of MUAL pups were significantly lower than sham. By 8 weeks, males but not females MUAL mice achieved equivalent mean body weight to control. Placental labyrinth depth, volume, and placental gene expression of IGF-1 and 2 were significantly reduced by MUAL. In contrast, placental protein level of IGFBP-2 and 6 were significantly elevated in the MUAL. Genomic expression analysis demonstrated that MUAL pups significantly up-regulated genes that were associated with apoptosis and growth pathways.

CONCLUSION:

This novel mouse animal model of FGR using selective ligation recapitulates multiple characteristics of placental vascular insufficiency (PI) in humans. This is the first non-genetic mouse model of PI which offers its application in transgenic mice to better study the underlying mechanisms in PI.

CONDENSATION:

A new mouse model of placental vascular insufficiency by selective ligation of mesenteric uterine artery branch recapitulates multiple findings observed in human placental vascular insufficiency.

KEYWORDS:

Fetal growth restriction; IGF; Mice animal model; Placental insufficiency

PMID:
24119485
DOI:
10.1016/j.placenta.2013.09.011
[Indexed for MEDLINE]
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