Objective: Paroxetine is an antidepressant known to have adverse impacts on the female reproductive system, while irisin is an exercise-induced adipo-myokine expected to alleviate these negative effects. This study aimed to explore the effects of paroxetine and/or irisin on the count of uterine mast cells (uMCs) and crucial reproductive hormones—17β-estradiol and progesterone—important for uMC physiology in adult female rats.

Materials and Methods: 40 adult female rats were divided into four groups (n=10 per group): sham vehicle, paroxetine, irisin, and paroxetine+irisin. The paroxetine and paroxetine+irisin groups were administered paroxetine (20 mg/kg/day via oral gavage) for eight weeks, and irisin (100 ng/kg/day, s.c.) was given using mini-osmotic pumps to irisin and paroxetine+irisin groups for the last four weeks of the eight-week study period. Serum hormone levels were quantified using the ELISA method. Uterine tissue samples underwent histochemical staining to detect uMCs using toluidine blue (TB) staining and a combined alcian blue safranin O (AB/SO) technique.

Results: The counts of AB (+) uMCs significantly increased in the paroxetine+irisin group vs the sham vehicle (p<0.05). Paroxetine treatment alone significantly increased TB (+) uMCs in the paroxetine group vs the sham vehicle (p<0.01). The paroxetine+irisin group also showed a significant increase in the TB (+) uMCs count vs sham vehicle (p<0.05). The count of SO (+) uMCs showed no significant change across groups. No alterations were observed in serum 17β-estradiol or progesterone levels due to either treatment.

Conclusion: It seems that irisin has no effect on uMCs or their subtypes. However, the effect of paroxetine on certain uMC subtypes in rat uterine tissue indicates that serotonin (5-HT) induced by paroxetine might have a role in regulating the uterine microenvironment.