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Toxicol Ind Health. 2014 Mar;30(2):174-81. doi: 10.1177/0748233712452603. Epub 2012 Jul 9.

Histomorphological and ultrastructural changes of the placenta in mice exposed to formaldehyde.

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Division of Anatomy and Histology, Department of Basic Sciences, Faculty of Para-Veterinary Medicine, University of Ilam, Ilam, Iran.


Formaldehyde (FA) is widely used in industrial and medical settings. It has long been suspected of causing adverse reproductive and developmental effects. However, the effects of exposure to FA on the reproduction are still a matter of scientific controversy. In this study, we evaluate the hypothesis that adverse developmental outcomes of the exposure to FA might be due to its effects on the placental structure. So, histological changes of the placenta in the mice exposed to FA gas were assessed at light and electron microscopy levels. A total of 40 pregnant Balb/C mice were randomly allotted to four groups in which the animals were exposed to FA at the doses of 0 (control), 7, 14 and 28 ppm, respectively, by inhalation, consecutively, for 8 h/d during the organogenesis period. On day 17 of gestation, the animals were killed and the histological specimens of the placentas were taken for light and electron microscopy studies. Also, morphological parameters of the placentas were measured manually. The results showed that the effects of FA on the placenta are not dose dependent. In the FA-exposed mice, an increase in the number and size of trophoblastic giant cells and an enlargement of spongiotrophoblastic cells in the basal zone of placenta were seen. Also, a significant increase in placental weight as well as the ratio of placental to fetal weight but a decrease in the fetal weight were found in the treated groups when compared with those in the control mice (p < 0.05). Moreover, ultrastructural results demonstrated that the diameter of labyrinth interhemal membrane as well as the thickness of trophoblastic basement membranes were significantly increased in the FA-exposed mice. In addition, in the FA-treated animals, a severe accumulation of cytoplasmic droplets in the II and III trophoblastic layers of the placenta were seen. In conclusion, this study may suggest that the exposure to FA during the organogenesis period at doses of 7-28 ppm induces toxic changes in the placental structure. These changes disrupt placental functions and leads to a decrease in the fetal weight.


Histomorphology; formaldehyde; mice; placenta; ultrastructure

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