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MicroRNA 200b is upregulated in the lungs of fetal rabbits with surgically induced diaphragmatic hernia
Author(s) -
Eastwood Mary Patrice,
Deprest Jan,
Russo Francesca Maria,
Wang Hongmei,
Mulhall Drew,
Iwasiow Barbara,
Mahood Thomas H.,
Keijzer Richard
Publication year - 2018
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.5318
Subject(s) - congenital diaphragmatic hernia , fetus , lung , diaphragmatic hernia , medicine , pulmonary sequestration , in situ hybridization , downregulation and upregulation , fetoscopy , andrology , gestational age , pathology , anatomy , hernia , biology , gene expression , surgery , prenatal diagnosis , pregnancy , genetics , biochemistry , gene
Objective Profiling of miR‐200b expression and its targets (transforming growth factor [TGF]–β2 and ZEB2) in the surgical rabbit congenital diaphragmatic hernia (DH) model before and after tracheal occlusion (TO). Methods Thirty‐eight timed‐pregnant rabbits had left DH creation on gestational day (GD) 23. On GD28, 17 randomly selected fetuses had TO. We harvested fetuses at GD23, GD28, or GD30. We calculated lung–to–body weight ratios, processed lungs for miR‐200b in situ hybridization and real‐time quantitative polymerase chain reaction, and evaluated effects on downstream targets TGF‐β2 or ZEB2. Results We obtained 16 DH fetuses (n = 7 GD28 and n = 9 GD30), 13 TO fetuses (GD30), and 38 control fetuses (n = 15 GD23, n = 11 GD28, and n = 12 GD30). Diaphragmatic hernia lungs were hypoplastic, and TO resulted in control lung–to–body weight ratio levels. Term miR‐200b‐3p levels were significantly upregulated in the hypoplastic compared with control ipsilateral lung (1.906 ± 0.90 vs 0.7429 ± 0.44) ( P < .01). Fetal TO ipsilateral lungs displayed a variable miR‐200b response on in situ hybridization and polymerase chain reaction, with levels similar to control and congenital DH lungs. The TGF‐β2 was unchanged in hypoplastic and TO lungs, and ZEB2 tended to be reduced in TO compared with DH lungs (1.79 [0.4‐2.9] vs 0.73 [0.5‐1.4]). Conclusions Hypoplastic fetal rabbit lungs display upregulation of miR‐200b expression although downstream targets are not different from controls. Following TO, fetal rabbit lungs display a variable miR‐200b response.