DYNAMIC CHANGES IN THE THALAMIC PROTEOME IN FETAL GROWTH RESTRICTED PIGLETS REVEALS EARLY NEUROPROTECTIVE RESPONSES FOLLOWED BY A DECLINE IN OXIDATIVE PHOSPHORYLATION

Fetal growth restriction (FGR) results from prolonged deficits in oxygen and nutrient supply, preventing the fetus from achieving its genetic growth potential. This condition is strongly associated with long-term neurodevelopmental deficits. Proteomic analysis provides a powerful approach for mapping the developing brain’s protein landscape and identifying expression patterns disrupted by FGR.
Term-born piglets were euthanised on postnatal day (PND) 1 (n = 23) or reared until PND10 (n = 22). Postmortem, piglets were classified as normally grown (NG) or FGR using a brain-to-liver weight ratio ≥ 1 (PND1) or brain-to-body weight ratio ≥ 1 (PND10). The thalamus was dissected for proteomic profiling, followed by pathway analysis. Selected proteins were validated by Western blot.
Proteomic analysis identified 82 upregulated and 83 downregulated proteins in FGR relative to NG at PND1, while at PND10, 58 proteins were upregulated and 50 downregulated. At PND1, the bioinformatic analysis did not detect hallmark pathological features of FGR, such as inflammation or oxidative stress. Instead, the thalamus appeared relatively preserved, with upregulation of translational pathways suggestive of early neuroprotective responses. These compensatory mechanisms diminished by PND10, where pathway analysis indicated mitochondrial dysfunction, marked by downregulation of oxidative phosphorylation. Western blot validation of ribosomal proteins (e.g., RPL3) or neuropathological markers (e.g., GFAP), confirmed similar protein expression trends, supporting the proteomic findings.
Future work will isolate ribosomal and mitochondrial fractions to further characterize the mechanisms driving early neuroprotection and subsequent pathology. Understanding these processes may support the development of therapeutic strategies for infants at risk of neurological impairment.