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Published on: August 6, 2014
Effect of chronic low dose of methotrexate on cellular proliferation during spermatogenesis in rats
A K Saxena1, S Dhungel, S Bhattacharya
1Human Cytogenetics Laboratory, Department of Anatomy, B.P. Koirala Institute of Health Sciences, Dharan-Nepal. draksaxena1@rediffmail.com
Abstract:
This study was conducted to evaluate cellular proliferation of germinal and non-germinal elements of seminiferous tubules following continuous Day 1 to Day 17 exposure of methotrexate (12.5 microgram) in male rats. There was significant decrease in the diameter of seminiferous tubules (P < 0.10) followed by increase of interstitial space (P < 0.01). The size of various stages of primary, secondary spermatocytes, and spermatids was altered significantly compared to controls. Vacuolization/decondensation of "chromatin-mass" in spermatocytes changed from rounded to oval. The size of the Sertoli and Leydig cells were reduced significantly. Basement membrane at some places seems to be disrupted and thin in experimental testis. Methotrexate induced cytotoxicity on the proliferation of cellular contents of seminiferous tubules elucidating the mechanism of dose-dependent drug induced testicular damage during spermatogenesis.
Insights
Methotrexate exposure significantly damages male rat testes, reducing seminiferous tubule diameter and altering germ cell size. This study reveals methotrexate
Area of Science:
- Reproductive toxicology
- Spermatogenesis research
- Cellular biology
Background:
- Methotrexate is a chemotherapy agent with known reproductive side effects.
- Understanding its impact on testicular cellular proliferation is crucial for managing treatment toxicity.
Purpose of the Study:
- To evaluate the effects of continuous methotrexate exposure on germinal and non-germinal elements in rat seminiferous tubules.
- To elucidate the mechanism of methotrexate-induced testicular damage during spermatogenesis.
Main Methods:
- Male rats were exposed to methotrexate (12.5 microgram) continuously from Day 1 to Day 17.
- Cellular proliferation and morphological changes in seminiferous tubules were assessed and compared to control groups.
Main Results:
- Significant decrease in seminiferous tubule diameter and increased interstitial space observed.
- Altered size of primary, secondary spermatocytes, and spermatids; vacuolization/decondensation of chromatin-mass in spermatocytes.
- Reduced Sertoli and Leydig cell size; disrupted and thinned basement membrane noted.
Conclusions:
- Methotrexate induces cytotoxicity affecting cellular proliferation within seminiferous tubules.
- The study elucidates a dose-dependent mechanism for drug-induced testicular damage during spermatogenesis.
