Article Text

  1. Z. Zarbock1,
  2. S. A. Jeffs1,
  3. R. A. McKnight1,
  4. S. L. Jenkins1,
  5. R. H. Lane1
  1. 1Division of Neonatology, Department of Pediatrics, Health Sciences Center, University of Utah, Salt Lake City, UT.


Background Intrauterine growth retardation (IUGR) predisposes human infants and children to infectious diseases. We have previously shown that IUGR decreases the overall number of lymphocytes and alters T-cell phenotype. IUGR has also been shown to affect males to a greater degree than females. The exact mechanisms underlying these effects are unknown; however, the growth factor insulin-like growth factor 1 (IGF-1) is known to play a significant role in thymic development and lymphocyte proliferation. Additionally, IGF-1 levels in other organ systems are altered by IUGR. Furthermore, IGF-1 has several splice variants, which are preferentially expressed due to epigenetic mechanisms known to be active in IUGR.

Objective We therefore hypothesized that IUGR would decrease thymic size and alter IGF-1 mRNA expression and its splice variants in male and female rat thymus.

Methods Bilateral uterine artery ligation was performed on pregnant Sprague-Dawley rats to induce IUGR. Thymus tissue was harvested from IUGR and sham controls and weighed at d0 and d21. mRNA levels of the IGF-1 transcription start sites P1 and P2, as well as splice variants IGF-1A and IGF-1B, were quantified with real-time RT-PCR.

Results At d0, male IUGR rat thymus had an average weight of only 0.0073 g ± 0.001 compared with sham at 0.0138 g ± 0.002 (p < .05, n = 5). d0 IUGR female thymus weighed 0.0075 g ± 0.0017 vs sham 0.012 g ± 0.0016 (p < .05, n = 6). Consistent with these findings, female IUGR rats at d0 showed increases in IGF-1 transcription initiation at P1 and P2, as well as an increase in the transcript encoding the IGF-1B peptide (p < .05). d21 females also showed an increase at the IGF-1A peptide (p < .05). Conversely, male IUGR rats at d0 did not show a significant difference in IGF-1 transcription initiation or splice variation. d21 IUGR males also did not show significant changes in IGF-1.

Conclusion The overall expression of IGF-1 was increased in IUGR female rat pups at d0 and the splice variant IGF-1A at d21. There were no significant changes in IGF-1 expression in male IUGR rat pups at d0 or d21. We know that IGF-1 is involved in the proliferation of lymphocytes and is increased in female IUGR rats and female lymphocyte phenotype and number are less affected by IUGR. We speculate that the increased IGF-1 levels and splice variants in females may explain why their immune systems are less severely affected by IUGR.

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