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Published on: January 10, 2025
Testis morphology in rats chronically treated with letrozole, an aromatase inhibitor
Anna Kondarewicz1, Agnieszka Kolasa, Bartosz Zawiślak
1Department of Histology and Embryology, Pomeranian Medical University in Szczecin, Poland. anna_kondarewicz@wp.pl
Abstract:
The aim of this study was to investigate the influence of the long-term treatment of rats with letrozole on the testis morphology. The pharmacologically induced estrogen deficiency caused statistically significant decreases of both intratesticular and serum levels of estradiol, and morphological changes in the seminiferous epithelium and in the interstitial tissue of the testes. Six months of treatment resulted in the sloughing of premature germ cells of the seminiferous epithelium into the tubular lumen and in intraepithelial vacuolization. Multinucleated giant cells composed of premature germ cells, conglomerates of various cell nuclei and cell debris as well as irregularities and infoldings of the tubular basement membrane were also seen. Moreover, deep invaginations of the lamina propria with myoid cells were observed. Cells in the interstitial tissue showed changes similar to that observed in aging processes. The cytoplasm of LH-R-positive Leydig cells was loaded with lipofuscin granules. The number of lipofuscin-loaded cells was significantly increased in the interstitial tissue of testis in letrozole-treated rats. The results indicate the direct influence of estrogens on seminiferous tubules and the interstitial tissue morphology.
Insights
Long-term letrozole treatment in rats caused significant testicular damage, including seminiferous epithelium changes and Leydig cell alterations. This highlights the crucial role of estrogens in maintaining testicular morphology and function.
Area of Science:
- Reproductive biology
- Endocrinology
- Histopathology
Background:
- Estrogens play a vital role in male reproductive health.
- Letrozole is an aromatase inhibitor that reduces estrogen levels.
Purpose of the Study:
- To investigate the long-term effects of letrozole-induced estrogen deficiency on rat testis morphology.
- To assess changes in seminiferous epithelium and interstitial tissue.
Main Methods:
- Rats were treated with letrozole for six months.
- Testis morphology was examined histopathologically.
- Intratesticular and serum estradiol levels were measured.
- Localization of luteinizing hormone receptor (LH-R)-positive Leydig cells was assessed.
Main Results:
- Letrozole treatment significantly decreased intratesticular and serum estradiol levels.
- Morphological changes observed included seminiferous epithelium damage (sloughing of germ cells, vacuolization) and interstitial tissue alterations.
- Increased lipofuscin accumulation in Leydig cells was noted, resembling aging changes.
Conclusions:
- Estrogen deficiency induced by letrozole has detrimental effects on testicular structure.
- Estrogens are essential for maintaining the integrity of seminiferous tubules and interstitial tissue.
- Long-term letrozole treatment may accelerate testicular aging processes.

