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Heart and Lung bta‐miR‐22‐3p Decrease and bta‐miR‐125a Increase in Growth‐restricted Fetal Lambs with Sustained in utero Stress
Author(s) -
Krauss Ramona,
Phipson Belinda,
Gupta Nikita,
Oshlack Alicia,
Cheung Michael,
Smolich Joseph,
Pepe Salvatore
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.814.11
Subject(s) - in utero , fetus , lung , microrna , andrology , biology , gestation , medicine , endocrinology , pregnancy , genetics , gene
Fetal cardiopulmonary development is a strictly regulated process that may be perturbed by intrauterine stress, but it is unknown whether such stress affects gestation‐related changes in heart or lung microRNA (miRNA) expression. We therefore measured cardiopulmonary miRNA expression in normal preterm (gestation=124‐129 days) and near‐term (gestation=139‐141 days; term=147 days) fetal lambs, and those with spontaneous and sustained in utero stress, evidenced by growth restriction and intense meconium staining. Total expression of known sheep miRNAs and miRNAs homologous with other species were profiled in lung, main pulmonary artery, left ventricular (LV) and right ventricular tissues (n=3‐5/group) by Illumina HiSeq next‐generation deep sequencing (NGS). miRNA expression in sheep exposed to in utero stress and controls was contrasted by empirical Bayes t‐statistics and validated by quantitative Real‐Time PCR. NGS analysis detected >1300 miRNAs in all tissues. Overall, miRNA profiles changed little with in utero stress. However, LV bta‐miR‐125a was 85% higher in near‐term fetuses with in utero stress (FDR=9.6%). By contrast, a decrease (FDR<5%) in bta‐miR‐22‐3p occurred in lungs (by 75%, p=0.001) and LV (by 50%, p=0.005) of preterm fetuses and lungs (by 65%, p=0.002) of near‐term fetuses with in utero stress. As these miRNAs have critical roles in differentiation, proliferation, and cell growth, their specific actions in models of in utero stress now require direct study.