Postnatal persistence of nonhuman primate sex-dependent renal structural and molecular changes programmed by intrauterine growth restriction

Andrew C. Bishop, Kimberly D. Spradling-Reeves, Robert E. Shade, Kenneth J. Lange, Shifra Birnbaum, Kristin Favela, Edward J. Dick, Mark J. Nijland, Cun Li, Peter W. Nathanielsz, Laura A. Cox

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Poor nutrition during fetal development programs postnatal kidney function. Understanding postnatal consequences in nonhuman primates (NHP) is important for translation to our understanding the impact on human kidney function and disease risk. We hypothesized that intrauterine growth restriction (IUGR) in NHP persists postnatally, with potential molecular mechanisms revealed by Western-type diet challenge. Methods: IUGR juvenile baboons were fed a 7-week Western diet, with kidney biopsies, blood, and urine collected before and after challenge. Transcriptomics and metabolomics were used to analyze biosamples. Results: Pre-challenge IUGR kidney transcriptome and urine metabolome differed from controls. Post-challenge, sex and diet-specific responses in urine metabolite and renal signaling pathways were observed. Dysregulated mTOR signaling persisted postnatally in female pre-challenge. Post-challenge IUGR male response showed uncoordinated signaling suggesting proximal tubule injury. Conclusion: Fetal undernutrition impacts juvenile offspring kidneys at the molecular level suggesting early-onset blood pressure dysregulation.

Original languageEnglish (US)
Pages (from-to)329-344
Number of pages16
JournalJournal of medical primatology
Volume51
Issue number6
DOIs
StatePublished - Dec 2022
Externally publishedYes

Keywords

  • IUGR
  • caloric mismatch
  • kidney
  • nonhuman primate

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

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