Diclofenac is a non-steroidal anti-inflammatory drug widely used by the general population and, although generally contraindicated during pregnancy, it is also used by some pregnant women. This study investigated endocrine, reproductive and behavioral effects of diclofenac in male and female offspring rats exposed in utero from gestational days 10–20. Pregnant rats were treated with diclofenac at doses of 0.2, 1 and 5 mg/kg/day via oral gavage. Anogenital distance (AGD), number of nipples, and developmental landmarks of puberty onset - vaginal opening (VO), first estrus (FE) and preputial separation (PPS) – were evaluated in the offspring. At adulthood, behavioral and reproductive parameters were assessed. Male and female rats were tested in the elevated plus maze test to assess locomotor activity and anxiety-like behaviors, while male rats were also evaluated in the partner preference test. No significant effects were observed on AGD and number of nipples in both males and females. Diclofenac treatment induced an overall delay in developmental landmarks of puberty onset in male and female offspring, which reached statistical significance for PPS at the lowest diclofenac dose. Prenatal exposure to all tested doses abolished the preference of male rats for an estrous female, suggesting an impairment of brain masculinization. No changes were observed on male or female reproductive parameters at adulthood. Overall, our results indicate that prenatal exposure to therapeutically relevant doses of diclofenac may have an impact in the pubertal development of rats and negatively affect male partner preference behavior.

双氯芬酸是一种非甾体类抗炎药，被普通人群广泛使用，虽然通常在怀孕期间禁用，但也有一些孕妇使用。本研究调查了双氯芬酸对子宫内暴露的雄性和雌性后代大鼠的内分泌、生殖和行为影响从妊娠 10-20 天开始。怀孕大鼠通过口服强饲法以 0.2、1 和 5 mg/kg/天的剂量用双氯芬酸治疗。在后代中评估肛门生殖器距离 (AGD)、乳头数量和青春期开始的发育标志 - 阴道开口 (VO)、第一次发情 (FE) 和包皮分离 (PPS)。在成年期，评估行为和生殖参数。雄性和雌性大鼠在高架十字迷宫测试中进行了测试，以评估运动活动和焦虑样行为，而雄性大鼠也在伴侣偏好测试中进行了评估。男性和女性的 AGD 和乳头数量均未观察到显着影响。双氯芬酸治疗导致雄性和雌性后代青春期发育标志的总体延迟，在最低双氯芬酸剂量下达到 PPS 的统计学意义。产前暴露于所有测试剂量消除了雄性大鼠对发情雌性的偏好，表明大脑男性化受损。成年期男性或女性生殖参数未观察到变化。总体而言，我们的结果表明，产前暴露于治疗相关剂量的双氯芬酸可能会对大鼠的青春期发育产生影响，并对男性伴侣的偏好行为产生负面影响。