Lack of Kidney Injury Sex Differences in Unilateral Ureter Obstructed Mice

Background: Renal fibrosis is a critical pathophysiological event in chronic kidney disease. Unilateral ureteral obstruction (UUO) is a well-established and widely used model for investigating renal fibrosis. Because the UUO surgery is difficult to conduct in female mice, there are limited studies to evaluate UUO kidney injury sex differences in mice.The goal of this experimental study is to compare renal injury caused by UUO in wild-type and renal hypoplasia low nephron number mice. Method: Male and female C57Bl/J6 wild-type (WT) and ROP/Le- Os Ces1ca/+ Ces1ca/J oligosyndactyl (ROP Os/+) mice were subjected to UUO or sham surgery, and kidney tissue collected at the end of the 10-day experimental period. Kidney histological analysis and mRNA expression determined renal fibrosis, tubular injury, collagen deposition, extracellular matrix proteins, and immune cell infiltration. Results: Our data demonstrated marked renal injury, fibrosis, and extracellular matrix production in the kidneys of male and female UUO WT and ROP Os/+mice. Renal cortical fibrosis was 16.8 ± 2.3% in male and 17.3 ± 1.6% in female UUO WT mice. ROP Os/+ UUO kidney cortical fibrosis averaged 9.1 ± 1.6% in male and 10.3 ± 1.3% in female mice. Kidney immunohistochemical staining for α-smooth muscle actin (a-SMA) averaged 4.7 ± 0.8% in male and 4.1 ± 0.5% in female UUO WT mice and 3.1 ± 0.4% in male and 2.8 ± 0.3% in female UUO ROP Os/+ mice. Kidney mRNA expression of a-SMA, fibronectin (Fn1), and ZEB-1 was increased to a similar degree in male and female WT and ROP Os/+ mice following UUO. UUO increased renal expression of a-SMA, Fn1, and ZEB-1 to a greater degree in UUO ROP Os/+ compared to UUO WT mice. Kidney immunohistochemical analysis of MAC2 was conducted in male and female WT and ROP Os/+ mice following UUO. Renal MAC2 levels were increased to a similar extent in male and female UUO WT, and male and female UUO ROP Os/+ mice compared to their respective sham operated control groups. Interestingly, renal inflammation phenotypes following UUO were 30-45% greater in WT compared ROP Os/+ mice. Summary: These findings demonstrate UUO induced kidney fibrotic injury did not exhibit sex difference in WT or ROP Os/+ mice. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.