The interruption of the treatment with naproxen restored the C57BL/6 ovulation rate

Naproxen is a widely used nonsteroidal anti-inflammatory drug, and previous studies have shown that its administration in mice influenced antral follicle growth and ovulation. Therefore, the present study aimed to investigate the reversibility of these effects following treatment interruption and to evaluate their impact across different mouse backgrounds. For Experiment I, C57BL/6 females (n = 20, 6 weeks of age) were treated with 10 mg/kg (low, n = 7) or 50 mg/kg (high, n = 7) of naproxen, while animals of the vehicle group received PBS + DMSO 5% (n = 6), followed by 21 days of rest. After euthanasia, the ovaries were histologically analysed. For Experiment II (C57BL/6) and Experiment III (Swiss and BALB/c), animals were treated for eight days with the same protocol, receiving 20 IU of eCG and 20 IU of hCG for ovulation induction. Recovered oocytes were collected and quantified. Results demonstrated that the treatment affected the percentage of primary follicles, which increased in the high-dose group compared with the vehicle group. Additionally, the rate of antral follicles was higher in the high group than in the vehicle and low-dose groups. The number of ovulated oocytes was not altered in BALB/c and Swiss females, as well as the number of corpora haemorrhagica and corpus luteum (p > 0.05). Overall, our findings indicate that naproxen treatment may have transient effects on folliculogenesis in C57BL/6 mice, with no impact in BALB/c or Swiss mice.