Nicotine- or epinephrine-induced uteroplacental vasoconstriction and fetal growth in the rat
Abstract
We examined the relationship between nicotine-induced vasoconstriction in pregnant rat dams and fetal growth during the third trimester of pregnancy. Pregnant rats were continuously treated between days 13 and 19 of gestation with either nicotine (9.6, 4.8 or 2.4 mg/kg/day), epinephrine (0.72 microgram/kg/day), or saline via continuous infusion from a subcutaneously implanted osmotic minipump. Placental weights in rats treated with high dose nicotine and dams' body weights were severely reduced. However, fetal weights were not affected. Blood flows in uterus and placenta were quantified by measurement of tissue content of 85Sr-labelled microspheres injected via a carotid artery catheter. Both nicotine and epinephrine caused a significant reduction (> 40%) in uterine and placental blood flow. We conclude that vasoconstriction alone as a result of nicotine or epinephrine administration during the last trimester of gestation does not necessarily reduce nutrient supply to the fetus and does not affect fetal growth in rats.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Animal models using nicotine alone do not show a consistent effect on fetal growth at exposures that model typical smokers.
“animal models utilizing nicotine alone do not demonstrate any consistent effect on fetal growth at exposures modeling those in typical smokers.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [41]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cited by
Sorted by citations
Risks and Benefits of Nicotine to Aid Smoking Cessation in Pregnancy
Dempsey, D. A., & Benowitz, N. L. (2001) · Drug Safety · doi:10.2165/00002018-200124040-00005 · Cited by 346 · see citing works
“This is in contrast to nicotine administration which results in reduced maternal weights at doses that do not reduce fetal weight.[72,137,177] Bolus doses of nicotine by gavage or subcutaneous or intraperitoneal administration usually resulted in birthweight reduction, decreased litter size, and decreased survival.”
BackgroundResultHuman placenta: a human organ for developmental toxicology research and biomonitoring.
Myllynen, P., Pasanen, M., & Pelkonen, O. (2005) · Placenta · doi:10.1016/j.placenta.2004.09.006 · Cited by 252 · see citing works
England, L. J., Aagaard, K., Bloch, M., Conway, K., Cosgrove, K., Grana, R., Gould, T. J., Hatsukami, D., Jensen, F., Kandel, D., et al. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.11.013 · Cited by 181 · see citing works
“(36-39) In agreement with the latter finding, animal models utilizing nicotine alone do not demonstrate any consistent effect on fetal growth at exposures modeling those in typical smokers.(40-42) Together, these findings provide evidence that nicotine and other tobacco smoke components produce distinctive adverse pre…”
ResultVaglenova, J., Birru, S., Pandiella, N. M., & Breese, C. R. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2003.07.005 · Cited by 180 · see citing works
The Effects of Nicotine on Development
McGrath-Morrow, S., Gorzkowski, J., Groner, J., Rule, A., Wilson, K., Tanski, S., Collaco, J., & Klein, J. (2020) · Pediatrics · doi:10.1542/peds.2019-1346 · Cited by 148 · see citing works
Effects of maternal prenatal stress on offspring development: a commentary
Lazinski, M. J., Shea, A. K., & Steiner, M. S. (2008) · Archives of Women s Mental Health · doi:10.1007/s00737-008-0035-4 · Cited by 120 · see citing works
“Other risk factors include lower socioeconomic status (SES), a family history of depression, and the experience of childhood neglect and abuse ( Bifulco et al. 1998; Wise et al. 2001; Robertson et al. 2004; Leigh and Milgrom 2008).”
BackgroundNicotinic acetylcholine receptors in rat and human placenta.
Lips, K., Brüggmann, D., Pfeil, U., Vollerthun, R., Grando, S., & Kummer, W. (2005) · Placenta · doi:10.1016/j.placenta.2004.10.009 · Cited by 115 · see citing works
“The nAChR in placental vessels are suggested to be involved in the cholinergic regulation of blood flow and fluid volume in placental vessels [29], where nicotine is known to cause a significant reduction in uterine and placental blood flow [32,50,51].”
BackgroundAlcohol, Methamphetamine, and Marijuana Exposure Have Distinct Effects on the Human Placenta.
Carter, R., Wainwright, H., Molteno, C., Georgieff, M., Dodge, N., Warton, F. L., Meintjes, E., Jacobson, J. L., & Jacobson, S. W. (2016) · Alcoholism: Clinical and Experimental Research · doi:10.1111/acer.13022 · Cited by 70 · see citing works
“Alcohol and nicotine exposure both produce placental vasoconstriction and a compensatory increase in perfusion pressure that can decrease oxygen delivery to the fetus (Birnbaum et al., 1994; Taylor et al., 1994).”
BackgroundThe effect of nicotine on developing brain catecholamine systems
Heather, S. (1999) · Frontiers in bioscience · doi:10.2741/oliff · Cited by 66 · see citing works
“Although some changes may be mediated indirectly via uteroplacental constriction and metabolic effects (177), it has been shown that nicotine can also significantly impact neurobehavioral development when administered by chronic infusion at doses that do not alter fetal growth (128).”
BackgroundDasu, M., Ramirez, S., La, T. D., Gorouhi, F., Nguyen, C., Lin, B. R., Mashburn, C., Stewart, H., Peavy, T., Nolta, J. A., et al. (2014) · Stem Cells Translational Medicine · doi:10.5966/sctm.2013-0200 · Cited by 35 · see citing works
Pesticides exposure through environment and risk of pre-term birth: a study from Agra city
Anand, M., Singh, L., Agarwal, P., Saroj, R. K., & Taneja, A. (2017) · Drug and Chemical Toxicology · doi:10.1080/01480545.2017.1413107 · Cited by 30 · see citing works
Zhou, J., Liu, F.-L., Yu, L., Xu, D., Li, B., Zhang, G.-H., Huang, W., Li, L., Zhang, Y.-Z., Zhang, W., et al. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.02.017 · Cited by 27 · see citing works
“…is a limitation in injection administration, as it is reported that an injection can trigger the release of catecholamines resulting in vasoconstriction and reduced blood flow (Birnbaum et al., 1994), so an adjustment should be made in the aspect of administration method in our future studies.”
MethodExposure to Nicotine During Pregnancy and Altered Learning and Memory in the Rat Offspring
Li, J., Bo, L., Zhang, P., Gao, Q., Li, L., Tang, J., Wu, C., Li, D., Xiao, J., Chen, J., et al. (2014) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntu178 · Cited by 25 · see citing works
Cigarette exposure induces changes in maternal vascular function in a pregnant mouse model.
Gandley, R., Jeyabalan, A., Desai, K. V., McGonigal, S., Rohland, J., & Deloia, J. (2010) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.00274.2009 · Cited by 19 · see citing works
The effect of nicotine on in vitro placental perfusion pressure.
Bainbridge, S., & Smith, G. N. (2006) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y06-037 · Cited by 19 · see citing works
Cetin-Atalay, R., Meliton, A., Wu, D., Woods, P. S., Sun, K., Peng, Y.-J., Nanduri, J., Su, X., Fang, Y., Hamanaka, R., et al. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.701995 · Cited by 18 · see citing works
Mao, C., Yuan, X., Zhang, H., Lv, J., Guan, J., Miao, L., Chen, L., Zhang, Y., Zhang, L., & Xu, Z. (2008) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2008.02.007 · Cited by 18 · see citing works
“ChAT mRNA expression was detected in spinal cord, septal area, striatum, cortex, and hippocampus in neonatal and adult rat CNS (Cavicchioli et al., 1991).”
BackgroundInfluentialLacy, R. T., Mactutus, C. F., & Harrod, S. B. (2011) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2010.12.001 · Cited by 17 · see citing works
“Furthermore, Birnbaum et al. (1994) utilized a continuous nicotine exposure model and reported a ∼40% reduction in uterine and placental blood flow with doses at least 15-fold higher than the dose in the present model.”
InfluentialAprioku, J. S., & Ugwu, T. (2015) · International Journal of Reproductive Medicine · doi:10.1155/2015/676245 · Cited by 15 · see citing works
“Reproductive dysfunction is a major cause of infertility among couples and tobacco smoke has been shown to cause different forms of reproductive dysfunction in both male and female: low birth weight [14, 15], prenatal and neonatal mortality [16], reduction in uterine blood flow [17, 18], and reduced penile erection [1…”
BackgroundAnand, M., Agarwal, P., Singh, L., & Taneja, A. (2015) · Toxicology Research · doi:10.1039/c4tx00094c · Cited by 14 · see citing works
Is grand-parental smoking associated with adolescent obesity? A three-generational study
Dougan, M., Field, A., Rich-Edwards, J., Hankinson, S., Glynn, R., Willett, W., & Michels, K. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.186 · Cited by 11 · see citing works
“Prenatal exposure to smoking may affect the development of these oocytes as the vaso-constrictive effects of nicotine and cotinine may impair blood flow to the developing fetal ovary (17, 18).”
BackgroundSmoke signals in the genome: Epigenetic consequences of parental tobacco exposure (Review)
Vlachou, M., Kyrkou, G., Georgakopoulou, V., Kapetanaki, A., Vivilaki, V., Spandidos, D. A., & Diamanti, A. (2025) · Biomedical Reports · doi:10.3892/br.2025.2024 · Cited by 10 · see citing works
Anto, S., Koyada, N., Khan, S., & Jena, G. (2016) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2015-0151 · Cited by 10 · see citing works
Remodeled salt appetite in rat offspring by perinatal exposure to nicotine.
Hui, P., Rui, C., Liu, Y.-J., Xu, F.-C., Wu, J., Wu, L., Chen, Y., Liao, J., Mao, C., & Xu, Z.-C. (2009) · Appetite · doi:10.1016/j.appet.2008.12.013 · Cited by 9 · see citing works
The effect of ethanol and nicotine on ER stress in human placental villous explants
Huovinen, M., Ietta, F., Repo, J. K., Paulesu, L. R., & Vähäkangas, K. (2022) · Current Research in Toxicology · doi:10.1016/j.crtox.2022.100081 · Cited by 8 · see citing works
“on placental blood flow have been studied in animals (Birnbaum et al., 1994) and in human placental perfusion (Bainbridge and Smith, 2006), but molecular toxicity in human placental tissue has not yet been studied.”
BackgroundSaroj, R. K., Anand, M., & Kumari, N. (2020) · Social Science Research Network · doi:10.22541/au.160691771.17181638/v1 · Cited by 6
Urîtu, A., Buciu, V.-B., Roi, C., Chioran, D., Șerban, D., Nicoleta, N., Rusu, E., Ionac, M., Riviș, M., & Ciurescu, S. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134773 · Cited by 5
“Although clinical data on vasoconstrictor safety in pregnancy remain limited, preclinical studies provide valuable mechanistic insights into their potential effects on uterine and placental physiology [40,41].”
Toxicological assessment of epinephrine and norepinephrine by analog approach.
Aydın, A., & Tugcu, G. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.06.028 · Cited by 4
Buschatz, D., Schlüter, B., Zernikow, B., & Trowitzsch, E. (1999) · Somnologie - Schlafforschung und Schlafmedizin · doi:10.1007/s11818-999-0019-2 · Cited by 3 · see citing works
Brenders, A., Bleeser, T., Deprest, J., Rex, S., & Devroe, S. (2024) · International journal of obstetric anesthesia · doi:10.1016/j.ijoa.2024.104287 · Cited by 3 · see citing works
Evaluating the control: minipump implantation and breathing behavior in the neonatal rat.
Kidder, I. J., Mudery, J. A., Barreda, S., Taska, D. J., & Bailey, E. (2016) · Journal of applied physiology · doi:10.1152/japplphysiol.00080.2016
Heart Rate Variability as a Measure of Depression and Anxiety during Pregnancy
Shea, A. K., Steiner, M. S., & Kamath, M. (2012) · CRC Press eBooks · doi:10.1201/b12756-30
- Authors
- Birnbaum, S. C., Kien, N., Martucci, R. W., Gelzleichter, T. R., Witschi, H., Hendrickx, A. G., & Last, J. A.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Last, Jerold A.
- ORCID
- Last, Jerold A.
- Venue
- Toxicology
- Publisher
- Elsevier BV
- Published
- 1994-11
- Volume
- 94
- Issue
- 1-3
- Pages
- 69-80
- ISSN
- 0300-483X (ISSN-L)
- OpenAlex
- W2011415011
- Cited by
- 37
- References
- 0
- Citations by year
- 2025: 2 · 2024: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 2 · 2012: 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (ES05707)
- National Center for Research Resources (P51RR000169, RR-00169)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- nicotine, epinephrine, fetal growth, placental blood flow, uterine blood flow, third trimester, placental weight, fetal nutrient supply, prenatal drug exposure, rat pregnancy
- MeSH terms
- Animals, Cotinine, Epinephrine, Female, Embryonic and Fetal Development, Fetus, Maternal-Fetal Exchange, Nicotine, Placenta, Pregnancy, Vasoconstriction, Infusion Pumps, Implantable, Rats, Sprague-Dawley, Placental Circulation, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
