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17 April 2017 Impact of gestational nicotine exposure on intrauterine and fetal infection in a rodent model
Maria von Chamier, Leticia Reyes, Linda F. Hayward, Mary B. Brown
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We investigated the interaction between prenatal nicotine exposure and intrauterine infection using established rat models. Beginning at gestation day (GD) 6, dams were continuously infused with either saline or 6 mg/kg/day nicotine (Nic). At GD 14, dams received either sterile broth or 105 colony-forming units Mycoplasma pulmonis (MP), resulting in four treatment groups: control (4 dams, 33 fetal units); MP only (5 dams, 55 fetal units); Nic only (5 dams, 61 fetal units), and Nic MP (7 dams, 82 fetal units). AtGD18, nicotine exposure significantly increased (P≤0.02) the percentage of amniotic fluids and fetuses infected by MP but did not impact colonization rates of maternal sites. Nicotine exposure significantly reduced the numbers of MP in the placenta required for high microbial loads (≥104 color-changing units) in the amniotic fluid (P < 0.01). Fetal inflammatory response lesions were most extensive in the Nic only and Nic MP groups (P < 0.0001). Control and MP only placentas were interleukin (IL)10-dominant, consistent with an M2/Th2 environment. Placentas exposed to nicotine shifted to a neutral environment, with equivalent levels of interferon gamma (IFNG) and IL10. Both IL6 and tumor necrosis factor (TNF) levels in amniotic fluid were highly elevated when both nicotine and infection were present. Our study suggests that prenatal exposure to nicotine increases the risk for intrauterine infection, lowers the infectious dose required to breach the placental barrier and infect the amniotic fluid and fetus, and alters the pathology and inflammatory profile associated with maternal and fetal sites.

Summary Sentence

A modifiable risk factor (nicotine) can directly impact what has been considered an immutable risk factor (infection) resulting in increased risk of pathogen transmission across the placental barrier with subsequent impacts on placental pathology and maternal/fetal immune environment.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please e-mail:
Maria von Chamier, Leticia Reyes, Linda F. Hayward, and Mary B. Brown "Impact of gestational nicotine exposure on intrauterine and fetal infection in a rodent model," Biology of Reproduction 96(5), 1071-1084, (17 April 2017).
Received: 18 November 2016; Accepted: 11 April 2017; Published: 17 April 2017

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