Effect of Chronic Low Dose of Methotrexate on Cellular Proliferation During Spermatogenesis in Rats

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.

The histopathological evaluation of healing effects of vitamin C administered before methotrexate therapy on testicular injury induced by methotrexate

“…[6,[14][15][16][17] Changes in dimensions of primary, and secondary spermatocytes alter the size of spermatids, and Leydig cells. [18] As indicated in available studies MTX damages seminiferous tubuli of testis with resultant decrease in sperm counts, and harmful effects on sperm DNA. Studies performed have demonstrated that MTX exerts its cellular effects by decreasing antioxidative effectiveness of cells, and exposes them to deleterious effects of reactive oxygen species (ROS) leading to destructive changes in testicular tissue, and germ cells.…”

The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis

“…MTX-induced toxicity is characterized by the formation of the inflammatory response due to the increased production : P < 0.0001 [1][2][3] : P < 0.001 [2][3] : P < 0.0049 [3][4] : P < 0.02778 Figure 2. A) Control group: the membrane propria (MP) surrounding the seminiferous tubules had a normal structure.…”

“…When the multinucleated giant spermatogenic cells in the MTX group were compared with those of the control group, there was a significantly greater number of them : P < 0.001 [3][4] : P < 0.059 1-2, 2-3, 2-4 : P < 0.001 [1][2][3] : P < 0.063 [3][4] : P < 0.048 (P = 0.0139). In other groups, these cells were few in number, not significantly different from the control group (P = 0.9345 for VEMTX, P = 0.1804 for LCMTX) ( Figure 1E).…”

“…The cells that are especially susceptible to these side effects are the ones that divide quickly, such as bone marrow, gastrointestinal mucosa, hair roots, and spermatogenic cells. Although gonadal injury is encountered frequently in MTX treatment, this side effect has been investigated less than the others (3,4).…”

Inflammatory bowel diseases and management considerations: Fertility and pregnancy

“…Other medications (eg, steroids, azathioprine, and infl iximab) appear safe in men with IBD who are trying to conceive. However, given limited data and evidence of altered spermatogenesis in animals [18,19], it is recommended to stop methotrexate at least 4 months before attempting conception.…”