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Kidney Week

Abstract: SA-PO0284

Gonadectomy Uncovers Sex-Dependent Mechanisms of Renal Compensation After Nephrectomy

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Stayton, Amanda Shea, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Patel, Prisha S., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Perales, Selene G., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Bridges, Jackson T., The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Zhang, Hongshan, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Pabla, Navjot, Stony Brook University, Stony Brook, New York, United States
  • Bajwa, Amandeep, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
Background

Sex-specific biological mechanisms critically influence the progression of kidney disease and recovery following renal injury; however, the contribution of gonadal hormones to adaptive renal compensation after nephron loss remains incompletely defined. In this study, we investigated whether gonadectomy differentially regulates compensatory renal function in male and female mice following nephrectomy using the resazurin dye assay as a functional measure of renal tubular secretion and adaptation.

Methods

Male and female mice underwent orchiectomy, oophorectomy, or corresponding sham procedures. Following a one-week recovery period, animals were subjected to either nephrectomy or sham surgery. Adaptive renal functional responses were subsequently evaluated using the resazurin assay as a quantitative measure of renal secretory function (Fig. 1A).

Results

Male mice exhibited a robust response to gonadectomy following nephrectomy. Orchiectomized males demonstrated significantly enhanced compensatory renal function relative to sham-operated nephrectomized controls, as evidenced by increased urinary resorufin excretion after nephrectomy (Fig. 1C). These findings indicate that removal of testicular hormones potentiates adaptive renal responses to nephron loss. In contrast, female mice showed a comparatively attenuated response to gonadectomy. In females, urinary resorufin levels were only modestly reduced in the oophorectomized/nephrectomized group compared with sham/nephrectomy controls, without evidence of a strong compensatory effect (Fig. 1B).

Conclusion

Gonadectomy induced sex-specific differences in renal compensation following nephrectomy, with orchiectomy enhancing tubular secretory function in male mice as evidenced by increased urinary resorufin excretion. These findings suggest that male gonadal hormones may impair adaptive renal responses to nephron loss and highlight sex hormone signaling as a key regulator of kidney adaptation and injury progression.

Funding

  • NIDDK Support