Effects of melatonin implants on uterine inflammation and ovarian progesterone receptor expression in female cats: A histopathological and molecular analysis

This study aimed to evaluate the histopathological and molecular effects of subcutaneous melatonin implants on the reproductive organs of female cats. Twenty cats were randomly divided into two groups: a control group (Cont), which underwent ovariohysterectomy without prior treatment, and a melatonin-treated group (Mel), which received 18 mg melatonin implants subcutaneously in the interscapular region before ovariohysterectomy. Histopathological and immunohistochemical analyses of uterine tissues were performed, along with quantitative RT-PCR and Western blot to assess inflammatory markers and progesterone receptor expression. Histopathological findings revealed normal uterine structures in most control cats, with mild inflammation observed in a few cases. In contrast, melatonin-treated cats exhibited varying degrees of uterine inflammation, ranging from mild to severe. Immunohistochemical analysis showed elevated IL-1 beta expression in the treated group compared to controls. Molecular analysis revealed significant upregulation of IL-6, TNF-alpha, NF-kB, IFN-gamma, ICAM-1, and iNOS in uterine tissues of the treated group (p < 0.05). Western blot analysis confirmed increased IL-6, TNF-alpha, NF-kB, IFN-gamma, and PGR protein expression in melatonin-treated cats, supporting inflammatory and hormonal alterations. Additionally, increased mRNA expression of progesterone receptor isoforms PR-A and PR-B was detected in ovarian tissues of melatonin-treated cats (p < 0.05). The results indicate that while melatonin implants effectively suppress estrus in female cats, they may induce uterine inflammation and alter the hormonal and immune profiles of reproductive tissues. These findings highlight the need for further investigation into the long-term safety and mechanisms of melatonin's effects on reproductive health.