LONG-TERM ACTIVATION OF MAST CELLS AS AN EXPERIMENTAL MODEL FOR STUDYING THEIR ROLE IN THE REGULATION OF SPERMATOGENESIS

Abstract

Mast cells are an important component of the immune microenvironment in the male reproductive system, involved in both physiological regulation and pathological processes through the secretion of various bioactive substances. Modeling dysregulation via activation or inhibition of mast cells and examining the impact on spermatogenesis can help clarify their exact role in its regulatory mechanisms. Ciprofloxacin, an antibiotic known to activate mast cells, has shown effectiveness for this aim in cardiac mast cell studies but has not been investigated in spermatogenesis. The aim of this study was to evaluate the effects of various ciprofloxacin regimens on mast cells in the reproductive organs of male Wistar rats and determine the optimal dose and duration for creating a model suitable for investigating mast cell involvement in spermatogenesis.

Materials and Methods. Male Wistar rats were treated with ciprofloxacin at 200 and 400 mg/kg for different durations. Morphological and functional characteristics of mast cells in the testes and epididymis were assessed histologically.

Results. Ciprofloxacin modulated mast cell activity in a time, dose, and tissue- dependent manner. A dose of 200 mg/kg for 7 days increased mast cell numbers, enhanced synthetic activity, and raised the proportion of cells with mature granules in both organs, while degranulation remained unchanged. This indicates a "preparatory" phase involving mast cell migration to reproductive tissues and granule accumulation. This was followed by active degranulation after 14 days, associated with return to baseline cell numbers, sustained high synthetic activity, and a predominance of mast cells with mature granules especially in the testes. The higher dose (400 mg/kg) accelerated mast cell activation, leading to earlier degranulation. While functional changes were consistent across both organs, morphometric parameters and granule maturation showed tissue-specific responses. Notably, testicular mast cells displayed minimal morphometric changes, possibly due to the immune - privileged nature of the testes.

Conclusions. Based on these findings, a 400 mg/kg dose for 7 days is recommended to induce mast cell activation for spermatogenesis studies. A 200 mg/kg dose is more suitable for pre-stimulation prior to the use of a degranulation inducer and for long-term studies to minimize potential side effects.