Effect of metronidazole on placental and fetal development in albino rats

Abstract

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.

Effect of the Aqueous Extract of Chrysobalanus icaco Leaves on Maternal Reproductive Outcomes and Fetal Development in Wistar Rats

“…In female rats, the process of implantation of the blastocyst in the endometrium occurs from the 1st to the 5th day of gestation and, during this period, the embryo is quite susceptible to lethality [ 40 ]. The success of pregnancy depends on the maintenance of progesterone and estrogen levels.…”

Editorial for the Special Issue: “Feature Papers in Drug Toxicity”

“…The last research article in this Special Issue, reported by Abdrabou et al ( contributor 9 ), showed that treatment with metronidazole, an antiprotozoal and antibacterial agent, during pregnancy induced teratogenicity and hepatoxicity and other fetal defects. Thus, metronidazole should be avoided during pregnancy, as another study showed the teratogenic effects with this compound in an animal model [ 10 ].…”

Exploration of Maternal and Fetal Toxicity Risks for Metronidazole-Related Teratogenicity and Hepatotoxicity through an Assessment in Albino Rats

“…Females are among the most vulnerable to being infected with vaginitis caused by parasites or pathologies related to childbirth and the care of women giving birth [1]. Intentionally or unintentionally, women rely broadly on medication or pharmaceutical therapy to treat protozoal and/or bacterial infections during pregnancy or when not pregnant [2].…”