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Beyond the uterine environment: a nonhuman primate model to investigate maternal-fetal and neonatal outcomes following chronic intrauterine infection.

ABSTRACT: BackgroundIntrauterine infection is a significant cause of early preterm birth. We have developed a fetal-neonatal model in the rhesus macaque to determine the impact of chronic intrauterine infection with Ureaplasma parvum on early neonatal reflexes and brain development.MethodsTime-mated, pregnant rhesus macaques were randomized to be inoculated with U. parvum (serovar 1; 105?c.f.u.) or control media at ~120 days' gestational age (dGA). Neonates were delivered by elective hysterotomy at 135-147?dGA (term=167d), stabilized, and cared for in our nonhuman primate neonatal intensive care unit. Neonatal reflex behaviors were assessed from birth, and fetal and postnatal brain magnetic resonance imaging (MRI) was performed.ResultsA total of 13 preterm and 5 term macaque infants were included in the study. Ten preterm infants survived to 6 months of age. U. parvum-infected preterm neonates required more intensive respiratory support than did control infants. MRI studies suggested a potential perturbation of brain growth and white matter maturation with exposure to intra-amniotic infection.ConclusionWe have demonstrated the feasibility of longitudinal fetal-neonatal studies in the preterm rhesus macaque after chronic intrauterine infection. Future studies will examine long-term neurobehavioral outcomes, cognitive development, neuropathology, and in vivo brain imaging to determine the safety of antenatal antibiotic treatment for intrauterine infection.

SUBMITTER: Kelleher MA

PROVIDER: S-EPMC5552412 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Beyond the uterine environment: a nonhuman primate model to investigate maternal-fetal and neonatal outcomes following chronic intrauterine infection.

Kelleher Meredith A MA Liu Zheng Z Wang Xiaojie X Kroenke Christopher D CD Houser Lisa A LA Dozier Brandy L BL Martin Lauren D LD Waites Ken B KB McEvoy Cindy C Schelonka Robert L RL Grigsby Peta L PL

Pediatric research 20170524 2

BackgroundIntrauterine infection is a significant cause of early preterm birth. We have developed a fetal-neonatal model in the rhesus macaque to determine the impact of chronic intrauterine infection with Ureaplasma parvum on early neonatal reflexes and brain development.MethodsTime-mated, pregnant rhesus macaques were randomized to be inoculated with U. parvum (serovar 1; 10<sup>5 </sup>c.f.u.) or control media at ~120 days' gestational age (dGA). Neonates were delivered by elective hysterotom ...[more]

PMID: 28422948

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Project description:Little is known about the repertoire of nonhuman primate kidney genes expressed throughout development. The present work establishes an understanding of the primate renal transcriptome at different stages of fetal development and defines the framework of gene expression in the context of renal maturation, which provides a basis for identifying deviations in transcriptome expression resulting from suboptimal conditions during renal development. The baboon kidney transcriptome was characterized at 60 days gestation (DG), 90DG, 125DG, 160DG and adulthood (6-12 years) using human genome arrays to identify differential gene expression in the context of biological pathways and hierarchical clusters. Whole genome expression profiling showed 11,331 genes that were expressed during kidney development, 4,698 of which were differentially expressed among the developmental time points. Pathway analysis indicated activation of annotated pathways previously reported to be important to kidney development and pathways not reported as relevant to kidney development. QRT-PCR for genes central to these pathways validated expression profiles and revealed differences between males and females at specific times in gestation. Hierarchical clustering indicated that two clusters best fit the data, one containing genes that increased in expression from 60DG to adult and one that decreased. Cluster analysis also revealed gene splice variants with discordant expression profiles during development. For example, SMAD4, which is central to Wnt signaling, TGF-β signaling and cell cycle, showed up-regulation of the full-length splice variant during development and down-regulation of a shorter variant that is missing DNA binding and protein heterotrimerization domains suggesting decreased inhibition of cell proliferation, which may impact renal cell number and maturation. This study provides the first detailed genetic analysis of the developing primate kidney, and our findings of discordant expression of gene splice variants suggest that gene arrays likely provide a simplified view and demonstrate the need to study the fetal renal proteome.

Dataset Information

Beyond the uterine environment: a nonhuman primate model to investigate maternal-fetal and neonatal outcomes following chronic intrauterine infection.

Publications

Beyond the uterine environment: a nonhuman primate model to investigate maternal-fetal and neonatal outcomes following chronic intrauterine infection.

Similar Datasets

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