Reduced placental size and increased apoptosis are associated with prenatal nicotine exposure in rats

A. Alzu’bi, M.S. Al Zoubi, G.T. Abdelhady, B. Al-Trad, S. Omari, M.I. Abualarjah, W. El-Huneidi, D.R. Alzu’bi, J.M. Bani-Issa, G.J. Clowry

Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan. ayman.alzubi@yu.edu.jo

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• Neonatology
• Obstetrics

OBJECTIVE: Smoking during pregnancy has been linked to a variety of negative embryonic and neonatal consequences. Nicotine is the major constituent of tobacco smoke, which was associated with adverse impacts on histological and functional features of the placenta. This study aims to investigate the potential influence of nicotine exposure on the rat placenta and fetus.

MATERIALS AND METHODS: Nicotine was administrated through the drinking water of female pregnant rats. The placental size, as well as the fetal body weight and size, were measured at E20. The mRNA expression of the Bax gene (pro-apoptotic), the Bcl-2 gene (anti-apoptotic) and the angiogenic genes VEGF, Flt-1, and HIF1 were measured in placental tissue. Furthermore, Immunohistochemistry (IHC) using Bax, caspase 9 and VEGF antibodies were performed on placental sections.

RESULTS: The results of the current study showed a significant reduction in the size of the placenta along with fetal body weight in nicotine treated group compared to the control group. Apoptosis was observed to be boosted in the placentas of the nicotine-treated group. This was associated with upregulation of Bax expression combined with no change in the expression of Bcl-2 in the treated group. On the other hand, there was no difference in the expression of angiogenic factors VEGF, Flt-1, or HIF1 between tested groups.

CONCLUSIONS: In utero nicotine exposure in pregnant rats showed deleterious impacts on fetus growth and weight, as well as placental size. These were accompanied by increased apoptosis within the placenta, as revealed by Bax gene upregulation.

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