ResearchObstetricsVitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates
Section snippets
Experimental design
Time-mated female Rhesus macaques (n = 27) were randomly allocated to control (n = 5), nicotine only (n = 4), vitamin C only (n = 9), or nicotine plus vitamin C groups (n = 9). On gestational day 26 of pregnancy, control animals received subcutaneous (midscapular) Alzet miniosmotic 2ML4 pumps containing bacteriostatic water (Abbott Laboratories, North Chicago, IL), and nicotine animals received subcutaneous osmotic minipump infusions of nicotine bitartrate (Sigma, St. Louis, MO) in
Results
Nicotine and cotinine levels in maternal serum, amniotic fluid, and cord blood at the time of delivery are shown in Table 1. Maternal plasma levels were similar in both groups. Nicotine and cotinine were undetectable in the amniotic fluid from control animals. Nicotine levels were significantly higher in the amniotic fluid of the vitamin C plus nicotine group, whereas cotinine showed a less notable increase, compared with the nicotine-only group.
Maternal, fetal birth, and placental weights are
Comment
We found that prenatal nicotine exposure significantly reduced overall fetal blood supply, which corresponded with significant histological findings characteristic of placental hypoxia. These effects were ameliorated in nicotine-exposed animals that received maternal vitamin C supplementation. The presence of nicotine, however, did not significantly alter maternal perfusion of the placenta.
Prenatal nicotine exposure has been associated with fetal hypoxia in utero.43 Our finding of decreased cQUV
References (58)
The influence of maternal nicotine exposure on neonatal lung metabolism: protective effect of ascorbic acid
Cell Biol Int
(1993)- et al.
Influence of maternal nicotine exposure on neonatal rat lung structure: protective effect of ascorbic acid
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol
(1997) - et al.
Nicotinic acetylcholine receptors in rat and human placenta
Placenta
(2005) Human placental cholinergic system
Biochem Pharmacol
(1997)- et al.
Umbilical artery flow velocity waveforms in high-risk pregnancy. Randomised controlled trial
Lancet
(1987) - et al.
Application of the steepest slope model reveals different perfusion territories within the mouse placenta
Placenta
(2013) - et al.
Comparative placental structure
Adv Drug Deliv Rev
(1999) - et al.
Intervillous blood flow in the third trimester gravid rhesus monkey (Macaca mulatta): use of sonographic contrast agent and harmonic imaging
Placenta
(2001) - et al.
Restriction of placental vasculature in a non-human primate: a unique model to study placental plasticity
Placenta
(2012) - et al.
Cigarette smoking and pregnancy I: ovarian, uterine, and placental effects
Placenta
(1999)
The adverse effects of maternal smoking on the human placenta: a review
Placenta
Antioxidants and fetal protection against ethanol teratogenicity. I. Review of the experimental data and implications to humans
Neurotoxicol Teratol
Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function
Am J Obstet Gynecol
A longitudinal study of quantitative uterine blood flow with the use of color power angiography in appropriate for gestational age pregnancies
Am J Obstet Gynecol
Cell type-specific expression and function of toll-like receptors 2 and 4 in human placenta: implications of fetal infection
Placenta
Low doses of nicotine-induced fetal cardiovascular responses, hypoxia, and brain cellular activation in ovine fetuses
Neurotoxicology
Influence of maternal tobacco smoking during pregnancy on uterine, umbilical and fetal cerebral artery blood flows
Early Hum Dev
Acute effect of oral vitamin C on coronary circulation in young healthy smokers
Am Heart J
Smoking in Dutch pregnant women and birth weight
Patient Educ Couns
Prenatal exposure to nicotine impairs nervous system development at a dose which does not affect viability or growth
Brain Res Bull
Nicotine patches for pregnant smokers: a randomized controlled study
Obstet Gynecol
Births: final data for 2002
Natl Vital Stat Rep
The effect of parental smoking on lung function and development during infancy
Respirology
Respiratory function among preterm infants whose mothers smoked during pregnancy
Am J Respir Crit Care Med
Levels of excess infant deaths attributable to maternal smoking during pregnancy in the United States
Matern Child Health J
Exposure to tobacco smoke in utero and the risk of stillbirth and death in the first year of life
Am J Epidemiol
The health consequences of smoking: nicotine addiction: a report of the Surgeon General. Department of Health and Human Services publication no. (Centers for Disease Control) 88–8406
Fetal toxicology of environmental tobacco smoke
Curr Opin Pediatr
Vitamin C prevents the effects of prenatal nicotine on pulmonary function in newborn monkeys
Am J Respir Crit Care Med
Cited by (21)
Effects of early daily alcohol exposure on placental function and fetal growth in a rhesus macaque model
2022, American Journal of Obstetrics and GynecologyCitation Excerpt :The placenta has a significant functional reserve to maintain adequate fetal nutrient delivery during pregnancy. However, when a critical threshold for placental compensation is reached,23,51 it can result in complications, such as intrauterine growth restriction, with increased fetal and neonatal mortality and morbidity.19 Thus, it is important to determine a noninvasive method to identify pregnancies at risk of hemodynamic alterations before the fetus is affected.
The effects of electronic cigarette vapor on placental trophoblast cell function
2018, Reproductive ToxicologyCitation Excerpt :However, to date there have been no animal or human studies which have specifically addressed the impact of e-cigarette use during pregnancy on fetal and obstetrical outcomes despite the fact that there is extensive evidence from animal and cell culture studies that nicotine, a common component of e-cigarette liquids and aerosols can cause placental dysfunction and/or impaired fetal growth [21,23]. Indeed, animal studies have shown that exposure to nicotine alone results in decreased placental blood flow, impaired placental blood vessel formation, reduced expression of placental angiogenic factors, deficits in trophoblast invasion and fetal growth restriction [21,54,55]. Early placentation requires extensive angiogenesis and trophoblast cell invasion of the maternal decidua to establish the feto-maternal circulation; impaired invasion and angiogenesis have profound effects on placental vascularization which in turn negatively impacts fetal development and growth [56,57].
Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP): Rationale, design, and methods of a randomized, controlled trial of vitamin C supplementation in pregnancy for the primary prevention of effects of in utero tobacco smoke exposure on infant lung function and respiratory health
2017, Contemporary Clinical TrialsCitation Excerpt :The data team then modifies the data with a full audit trail generated for each modification. Preliminary data in non-human primates has recently demonstrated decreased placental blood flow in nicotine-exposed fetal monkeys and has demonstrated that supplemental vitamin C decreases this effect [72]. Based on this data, an ancillary study funded NHLBI with co-funding from the Office of Dietary Supplements was obtained.
First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model
2017, American Journal of Obstetrics and GynecologyCitation Excerpt :Interestingly, at G135, fetal and placental outcomes are less severe. Although the mechanism for this discrepancy is unknown, it is consistent with placental adaptive capabilities to transient environmental perturbations as has been observed in early acute injury to macaque placentas46 when compared with chronic environmental perturbations throughout pregnancy.24,47 Although the placental weight in ethanol-exposed pregnancies compared with controls is less at G110, at G135 the placental weight was similar between both groups, which suggests that the placenta partly compensates by altering its growth trajectory to support fetal growth, albeit that fetal weights are not fully restored to control weights.
The effects of maternal smoking on pregnancy outcome and placental histopathology lesions
2016, Reproductive ToxicologyCitation Excerpt :Maternal smoking has been linked to numerous adverse outcomes including subfertility [1], miscarriages [2] and stillbirths [3], preterm premature rupture of membranes [4] and or delivery [5], placental abruption [6] and low birth weight [7], though, these outcomes are mostly amendable if smoking is ceased or even reduced [8]. Several trials have attempted to treat smokers with vitamin C during pregnancy to reduce perinatal morbidity [9], a beneficial effect also demonstrated in the placentas of treated patients [10]. It has been recently reported that 11% of patients smoke during pregnancy [11].
This study was supported by National Institutes of Health grants R01 HL087710, R21-HD076265, and P51 OD011092-53.
The authors report no conflicts of interest.
Cite this article as: Lo JO, Schabel MC, Roberts VHJ, et al. Vitamin C supplementation ameliorates the adverse effects of nicotine on placental hemodynamics and histology in nonhuman primates. Am J Obstet Gynecol 2015;212:370.e1-8.