da Silva Welma Emídio, de Melo Ismaela Maria Ferreira, de Albuquerque Yuri Mateus Lima, Mariano Aline Ferreira da Silva, Wanderley-Teixeira Valéria, Teixeira Álvaro Aguiar Coelho
Universidade Federal Rural de Pernambuco, Departamento de Morfologia e Fisiologia Animal, Recife, PE, Brasil.
Anim Reprod. 2019 Nov 18;16(4):810-818. doi: 10.21451/1984-3143-AR2018-0149.
Metronidazole is an antiprotozoal and antibacterial used in gynecology and obstetrics for the treatment of parasitic infections. However, despite having clinical use for more than three decades, questions about the safety of its use during pregnancy is not well understood. Thus, the present study evaluated the effect of metronidazole on placental and fetal development in pregnant rats. Metronidazole was orally administered by gavage at a dosage of 130 mg/kg for 7 and 14 days. Morphological analysis, morphometry and immunohistochemistry were performed at the implantation sites and placentas with 14 days of development. The results showed that in the treated group there was a significant reduction in the number of implantation sites, total placental disc area and constituent elements of the labyrinth and spongiotrophoblast layers. Histochemical analysis revealed no significant changes in the content of collagen, elastic and reticular fibers. The TUNEL test showed apoptotic activity in the implantation sites and placentas with 14 days of development independent of the treatment. There was no evidence of malformation in the neonates. However, there was a significant reduction in the number and weight of neonates in the group treated with metronidazole when compared to the control group. Thus, it is concluded that the administration of 130 mg/kg of metronidazole during pregnancy in rats, in addition to interfering with the number of implanted embryos, promotes changes in placental structure and interferes with fetal development. This suggests that this drug should be used with caution during pregnancy.
甲硝唑是一种抗原虫和抗菌药物，用于妇产科治疗寄生虫感染。然而，尽管其临床应用已超过三十年，但关于其在孕期使用的安全性问题仍未得到充分了解。因此，本研究评估了甲硝唑对孕鼠胎盘和胎儿发育的影响。通过灌胃以130mg/kg的剂量口服甲硝唑，持续7天和14天。在发育14天的着床部位和胎盘进行形态学分析、形态测量和免疫组织化学。结果显示，治疗组的着床部位数量、胎盘总盘面积以及迷路和海绵滋养层的组成成分均显著减少。组织化学分析显示，胶原、弹性和网状纤维含量无显著变化。TUNEL试验显示，发育14天的着床部位和胎盘存在凋亡活性，且与治疗无关。新生儿未出现畸形证据。然而，与对照组相比，甲硝唑治疗组的新生儿数量和体重显著减少。因此，得出结论，大鼠孕期给予130mg/kg甲硝唑，除了干扰着床胚胎数量外，还会促进胎盘结构变化并干扰胎儿发育。这表明该药物在孕期应谨慎使用。
