Agomelatine ameliorates abortion-related alterations in rats: Insights from behavioural, biochemical and histological...

Abortion aetiology is critically linked to increased myometrial contractions and maternal psychological stress. Given the limited efficacy of current therapies such as progesterone, investigating novel therapeutic interventions is essential. Melatonin exerts reproductive benefits. Agomelatine stands out as an agent that exerts antidepressant effects through serotonin receptor (5-HT_2C) antagonism in addition to its potent melatonergic activity. Furthermore, agomelatine inhibits myometrial contractions. In this context, this study investigates agomelatine's therapeutic potential in an abortion model across behavioural, biochemical and histological parameters. Eighty female Sprague-Dawley rats were randomized into eight groups: control, sham, abortion, melatonin (M), agomelatine (A), progesterone (P) and combinations (MP, AP). Following pregnancy (Day 0), oral treatments were administered daily for 14 days. Abortion was induced via mifepristone on Day 11. Depressive-like behaviours were assessed using a forced swimming test on Day 13. The next day, rats were sacrificed for serum hormone analysis and uterine histological evaluation. The forced swimming test showed shorter immobility time in the AP group compared to the abortion group. An enzyme-linked immunosorbent Assay revealed lower serum prostaglandin F_2α level in the AP group and lower serum oxytocin levels in the M, A, MP and AP groups versus the abortion group. Histologically, M, A, P, MP and AP groups exhibited higher scores for complete fetus, decidual congestion, decidual inflammation and cytotrophoblast-syncytiotrophoblast cells compared to the abortion group. Additionally, the abortion group showed higher decidual necrosis than controls. In conclusion, agomelatine-containing protocols demonstrated restorative effects in abortion across behavioural, biochemical and histological parameters. These effects of agomelatine provide a new perspective on the currently limited options for treatment of abortion.