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. 2018 Sep:229:311-315.
doi: 10.1016/j.jss.2018.04.028. Epub 2018 May 10.

Fetal tracheal occlusion in mice: a novel transuterine method

Emrah Aydin  1 , Rashika Joshi  2 , Marc Oria  3 , Brian Michael Varisco  2 , Foong-Yen Lim  3 , Jose Luis Peiro  3
Affiliations

Fetal tracheal occlusion in mice: a novel transuterine method

Emrah Aydin et al. J Surg Res. 2018 Sep.

Abstract

Background: Fetal tracheal occlusion (TO) is an emerging surgical therapy in congenital diaphragmatic hernia that improves the fetal lung growth. Different animal models of congenital diaphragmatic hernia and TO present advantages and disadvantages regarding ethical issues, cost, surgical difficulty, size, survival rates, and available genetic tools. We developed a minimally invasive murine transuterine TO model, which will be useful in defining how TO impacts lung molecular biology, cellular processes, and overall lung physiology.

Materials and methods: Time-mated C57BL/6 mice underwent laparotomy at embryonic day 16.5 (E16.5) with transuterine TO performed on two fetuses in each uterine horn. At E18.5, dams were sacrificed and fetuses harvested. The lungs of the TO fetuses were compared with the nonmanipulated counterparts by morphometric and histologic analysis.

Results: Successful TO was confirmed in 16 of 20 TO fetuses. Twelve of them survived to E18.5 (75%). Fetal weights were comparable, but lung weights were significantly greater in TO (28.41 ± 5.87 versus 23.38 ± 3.09, P = 0.043). Lung to body weight ratio was also greater (0.26 ± 0.003 versus 0.22 ± 0.002, P = 0.006). E18.5 TO lungs demonstrated dilated central and distal airspaces with increased cellularity. DNA/protein and DNA/lung weight ratios were elevated while protein/lung weight ratio was lower in TO compared to control.

Conclusions: Mice fetal transuterine TO is feasible with comparable outcomes to other current animal models. The increase in the lung weight, lung to body weight ratio and the DNA/protein ratio indicate organized lung growth rather than edema or cell hypertrophy.

Keywords: CHAOS; Congenital diaphragmatic hernia; Fetal lung development; Fetal tracheal occlusion; Lung growth; Mice.

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Conflict of interest statement

Financial disclosure: There is no financial disclosure to be declared.

Figures

Fig. 1 –
Fig. 1 –
(A) The transuterine bypassing of the suture through the neck. (B) Schematic representation of the transuterine suture through the neck, respecting one side vascular (carotid and jugular) elements and surrounding trachea. (a) The entrance of the needle. (b) The structures included by the suture. C = carotid artery; J = jugular vein; T = trachea; E = esophagus; V = vertebra.
Fig. 2 ‒
Fig. 2 ‒
Model characteristics. (A) Normalized fetal lung to body weight ratio. (B) Lung DNA to protein ratio. (C) Lung DNA, (D) RNA, and (E) protein content normalized to lung weight. Hematoxylin and eosin images of C57BL/6 E18.5 lungs (F) without (non-dilated airways) and (G) with (dilated airways) fetal transuterine tracheal occlusion.
See this image and copyright information in PMC

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