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Opposite effects of testosterone and estrogens on chronic allograft nephropathy
Balazs Antus1, Yousheng Yao, Erwei Song
1Department of Pathophysiology, Semmelweis Medical University, Budapest, Hungary.
Abstract:
In the present study we investigated whether donor gender or the effects of sex hormones play the greater role in the development of chronic allograft nephropathy. Kidneys of male and female Fisher rats were orthotopically transplanted into castrated male Lewis recipients. Animals were treated with testosterone, estradiol, or vehicle and the kidneys were harvested 20 weeks after transplantation for histological, immunohistological, and molecular analysis. Testosterone treatment resulted in increased proteinuria and profound glomerulosclerosis, irrespective of donor gender. In addition, mRNA levels of transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor-A and B (PDGF-A and B) chains were enhanced in these allografts. Estradiol reduced glomerulosclerosis and mononuclear cell infiltration in allografts of both genders that paralleled a decreased mRNA expression of TGF-beta1, PDGF-A and B. No donor gender-related differences were noted in vehicle-treated animals. Our findings demonstrate that sex hormones rather than donor gender have a significant impact on chronic allograft nephropathy.
Insights
Sex hormones significantly impact chronic allograft nephropathy, outweighing donor gender effects. Testosterone worsened kidney damage, while estradiol offered protection, highlighting hormonal influence in transplant outcomes.
Area of Science:
- Nephrology
- Immunology
- Endocrinology
Background:
- Chronic allograft nephropathy (CAN) is a major cause of kidney transplant failure.
- The roles of donor gender and sex hormones in CAN development are not fully understood.
Purpose of the Study:
- To investigate whether donor gender or sex hormones have a greater impact on chronic allograft nephropathy.
- To elucidate the specific effects of testosterone and estradiol on kidney allograft outcomes.
Main Methods:
- Orthotopic kidney transplantation from male and female Fisher rats to castrated male Lewis recipients.
- Post-transplant treatment with testosterone, estradiol, or vehicle.
- Histological, immunohistological, and molecular analyses of allografts at 20 weeks.
Main Results:
- Testosterone treatment increased proteinuria and glomerulosclerosis, regardless of donor gender, and elevated TGF-beta1 and PDGF mRNA levels.
- Estradiol treatment reduced glomerulosclerosis and inflammatory cell infiltration, correlating with decreased TGF-beta1 and PDGF mRNA.
- No significant donor gender differences were observed in vehicle-treated control groups.
Conclusions:
- Sex hormones, particularly testosterone and estradiol, play a more significant role in the development of chronic allograft nephropathy than donor gender.
- Hormonal modulation offers a potential therapeutic strategy for mitigating CAN progression.