Sex differences in renal mitochondrial respiration and renal function in adult intrauterine growth restricted rodents with MitoTEMPO treatment

Introduction: Intrauterine growth restriction (IUGR) affects 5-8% of pregnancies worldwide. IUGR increases the risk for kidney disease later in life, especially in males. One mechanism that may contribute to these sex differences is mitochondrial dysfunction. Mitochondrial dysfunction leads to oxidative stress accumulation, which can reduce glomerular filtration rate (GFR), a marker of kidney function. To determine if mitochondrial mediated oxidative stress reduces kidney function in IUGR offspring, we administered MitoTEMPO (MT), a mitochondria specific antioxidant. We hypothesize that IUGR rodents receiving MT will have enhanced renal function and improved mitochondrial function, with sex differences. Methods: Groups consisted of control (CON) male (M) ± MT, CON female (F) ± MT, IUGR M ± MT, and IUGR F ± MT. CON rats were from normal pregnant dams, and IUGR rats were from induced placental ischemic pregnant dams. Rats were weaned for 3 weeks then separated by sex and birth status. MT was given intraperitoneally (0.7mg/kg) daily for 14 days before terminal procedures. At 17-24 weeks (adulthood), kidney function was measured via glomerular filtration rate (GFR) with FITC-sinistrin. Renal mitochondrial respiration was measured via Oroboros Oxygraph by examining respiration of States 2-4. Results: State 2 and State 4 were unchanged among all groups. IUGR M ST3 decreased 30% compared to CON M (791±232 vs 1074±87 OCR pmol O 2 /sec/mg, ns). However, ST3 in IUGR M was improved with MT (1115±151 OCR pmol O 2 /sec/mg, ns). ST3 did not change in F groups. GFR did not change between CON and IUGR within each sex. MT increased GFR in CON M (2.8±0.7 vs 1.5±0.3 ml/min/100g BW, p< 0.05), CON F (1.1±0.2 vs 0.9±0.1 ml/min/100g BW, ns), and IUGR F (1.3±0.1 vs 0.9±0.1 ml/min/100g BW, p< 0.05) relative to nontreated groups. Although, MT given to IUGR M did not change GFR. Kidney weight did not change in CON M, IUGR M, or CON F relative to MT groups, but kidney weight increased with MT in IUGR F vs IUGR F (7±0.4 vs 6±0.1 Kidney g/1000g BW, p< 0.005). Conclusion: IUGR M exhibited a reduction in mitochondrial function and was improved by MT. There were no differences in GFR between CON and IUGR for either sex. GFR was enhanced in every group administered MT, except IUGR M. Therefore, MT can enhance kidney function in CON M and F and IUGR F but not IUGR M. Perhaps the ability of MT to increase GFR in IUGR F is due to an enlargement of the kidneys, allowing for an increase in nephron size and hyperfiltration. In summary, our findings differ from our original hypothesis but are novel and suggest exploring other mechanisms that may explain why there are sex differences in response to MT treatment. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.