Extrauterine support of pre-term lambs achieves similar transcriptomic profiling to late pre-term lamb brains

Abstract

Abstract Our group has developed an extra-uterine environment for newborn development (EXTEND) using an ovine model, that aims to mimic the womb to improve short and long-term health outcomes associated with prematurity. This study’s objective was to determine the histologic and transcriptomic consequences of EXTEND on the brain. Histology and RNA-sequencing was conducted on brain tissue from three cohorts of lambs: control pre-term (106–107 days), control late pre-term (127 days), and EXTEND lambs who were born pre-term and supported on EXTEND until late pre-term age (125–128 days). Bioinformatic analysis determined differential gene expression among the three cohorts and across four different brain tissue sections: basal ganglia, cerebellum, hippocampus, and motor cortex. There were no clinically relevant histological differences between the control late pre-term and EXTEND ovine brain tissues. RNA-sequencing demonstrated that there was greater differential gene expression between the control pre-term lambs and EXTEND lambs than between the control late pre-term lambs and EXTEND lambs (Supplemental Figs. 1 and 2). Our study demonstrates that the use of EXTEND to support pre-term lambs until they reach late pre-term gestational age results in brain tissue gene expression that more closely resembles that of the lambs who reached late pre-term gestation within their maternal sheep’s womb than that of the lambs who were born prematurely.

Keywords

• Prematurity
• Brain development
• RNAsequencing
• Gene set enrichment analysis
• Artificial womb