10/21/23, 9:15 AM Effect of E-cigarettes aerosol exposure during lactation in rats: Hormonal and biochemical aspects - ScienceDirect

Environmental Toxicology and Pharmacology

Volume 88, November 2021, 103759

Effect of E-cigarettes aerosol exposure during

lactation in rats: Hormonal and biochemical aspects
Nour A. Al-Sawalha a , Roba Bdeir b, Aiman Sohaib b, Marwan Saad a, Tasneem Inghaimesh a, Omar F. Khabour c
, Karem H. Alzoubi d e, Alan Shihadeh f g

a
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid,
Jordan
b Faculty of Pharmacy, Jadara University, Irbid, Jordan
c
Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan
d
Department of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, UAE
e Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan
f Mechanical Engineering Department, American University of Beirut, Beirut 1107 2020, Lebanon
g
Center for the Study of Tobacco Products, Virginia Commonwealth University, Richmond, VA, USA

Received 25 August 2021, Revised 7 October 2021, Accepted 20 October 2021, Available online 23 October 2021, Version
of Record 1 November 2021.

Edited by Dr. M.D. Coleman

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Abstract

Electronic cigarettes (e-cigarettes) have been marketed as a less lethal substitute for smoking traditional
cigarettes. This study aims to investigate the impact of e-cigarettes aerosol exposure on lactating dams and
pups, whose dams were exposed. Lactating dams received fresh air (control) or e-cigarettes aerosol during
lactation (day 4–21). Maternal exposure to e-cigarettes aerosol during lactation induced significant
reduction (P < 0.0001) in the fat content of the milk and serum Leptin level (P < 0.005) compared to control

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dams. Furthermore, pups whose dams were exposed to e-cigarettes during lactation showed an increased
level of glucose, thyroxine and decreased level of insulin. The exposure to e-cigarettes aerosol during
lactation altered the composition of milk as well as the hormonal and biochemical profile in dams and pups.
This result, if observed in women using e-cigarettes, suggests that e-cigarettes’ use during lactation may
have consequences on the milk production and hormonal and biochemical profile in breastfeeding mothers
and nursing babies.

Introduction

The smoking pandemic claims the lives of 7 million smokers and 1.2 million non-smokers who are exposed
to second-hand smoke annually ((WHO), 2021). Much effort has been made to reduce smoking and
encourage cessation through alternative and supposedly less harmful sources of nicotine as a form of
tobacco harm reduction (Rodu and Godshall, 2006). Electronic cigarettes (e-cigarettes), a relatively new
product that gained popularity worldwide, are handheld devices that produce an aerosol by heating a liquid
typically composed of propylene glycol, with or without glycerol, distilled water, flavorings, and nicotine
(Barbeau et al., 2013, Cheng, 2014). They are often marketed as a less lethal substitute for combustible
tobacco cigarettes (Pauly et al., 2007).

Research regarding the individual and population-level health effects of inhaling e-cigarettes aerosols is still
emerging. The long-term health effects of e-cigarettes use cannot be evaluated fully at this time because of
their relative novelty. In vivo studies using animal models have provided some insights into the biological
effects of exposure that cannot be studied in humans. Notwithstanding the harmful effects of smoking and
secondhand smoking on the fetus and infant development and health, a considerable number of women
continue to smoke during pregnancy and lactation or are exposed to smoke through secondhand smoking
from a smoking partner or the environment in general (Cnattingius, 2004, Higgins, 2002).

The American Academy of Pediatrics has documented the health benefits of breastfeeding on infants and
mothers and recommends breastfeeding for the first 6 months of an infant’s life (Eidelman and Schanler,
2012). Several studies have shown that nicotine is passed from the exposed mother to her breastfed baby
through lactation and breastmilk, and is shown to have adverse effects on fetus and child development
(Ward et al., 2001). In addition, exposure to nicotine can alter the composition of breast milk, such as
reduced iodine content (Laurberg et al., 2004), lower milk fats (Agostoni et al., 2003a, Szlagatys‐
Sidorkiewicz et al., 2013) and decreased in cytokine levels (Zanardo et al., 2005). Moreover, the amount of
nicotine transferred into breast milk reported as three times higher than that found in maternal blood
(Ferguson et al., 1976, Primo et al., 2013). Thus, there is a concern when it comes to maternal smoking
during pregnancy and lactation because the breastfed infants may be exposed to both second-hand aerosol
and chemicals transferred via breast milk.

Several experimental studies looked at the effects of nicotine exposure during lactation; and it is evident to
have short- and long-term effects on neonatal and child development. It is shown to disrupt the endocrine
system, leading to higher visceral adiposity, hypothyroidism, hyperleptinemia, specifically alterations in
leptin content on muscle and adipocytes (Pinheiro et al., 2011), and thus ultimately resulting overweight in
adulthood (Oliveira et al., 2010b, Santos-Silva et al., 2010). Moreover, metabolic programming is instantiated
with environmental stresses, such as maternal smoking or nicotine exposure as early events leading to

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down the line reverberations, for instance obesity (Lisboa et al., 2012a, Miranda et al., 2020b). Epigenetic
changes has been shown on several studies, linking the exposure of tobacco (Küpers et al., 2015, Suter et al.,
2010), as well as nicotine exposure (Wang et al., 2011), with changes in gene methylation profile and long-
term decrease in cortisol. Most recently, chen et al., (Chen et al., 2018), have found that e-cigarette exposure
during pregnancy and lactation adversely affected both pups’ and dams’ lung health in mice on account of
major changes in DNA methylation.

Thus, exposure to e-cigarette aerosol in general containing both nicotine and other smoke components,
rather than just nicotine exposure, may have different or combined effects in both hormonal and
biochemical profile in offspring. Therefore, in this study, we examine the effects of e-cigarettes aerosol
exposure on lactating dams and their milk, exposing dams to e-cigarette smoke during lactation separated
of their pups. Consequently, testing the effects of e-cigarette smoke components transferred only by milk.
We hypothesized that maternal exposure to e-cigarettes aerosol during lactation will alter the composition
of the milk as well as the biochemical and hormonal levels in dams and pups.

Section snippets

Animals

Forty-eight adult female and male Wistar rats (9–10 weeks old) were purchased from the Animal Care Unit
at Jordan University of Science and Technology (JUST). The animals were mated by placing one male and one
female rat in the same cage. Once pregnancy being confirmed, the rats were housed under controlled
temperature (24 ± 1 °C) and 12:12 light dark with free access to water and food until birth. The experimental
procedure was approved by Animal Care and Use Committee (ACUC) at JUST.…

Maternal exposure to e-cigarettes aerosol during lactation

Four days …

Effect of e-cigarettes aerosol during lactation on milk volume and composition

In milk (Table 1), the exposure to e-cigarette aerosol during lactation significantly reduced the fat content of
the milk (−11%, P < 0.0001). Protein content and milk volume showed substantial increases (16% and 19%
respectively) but neither increase was statistically significant. The milk’s lactose content was not affected by
exposure to e-cigarettes aerosol.…

Effect of e-cigarettes aerosol exposure during lactation on hormones

The levels of glucose and insulin in dams were not affected by e-cigarettes’ aerosol exposure. However, pups
whose dam were exposed to…

Discussion

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10/21/23, 9:15 AM Effect of E-cigarettes aerosol exposure during lactation in rats: Hormonal and biochemical aspects - ScienceDirect

The marketing of e-cigarette as a safer alternative to conventional cigarette smoking led to increased use
even during pregnancy and breastfeeding (Kaisar et al., 2016, Sapru et al., 2020). However, the amount of
nicotine that is consumed by e-cigarettes users can be similar to that consumed by conventional cigarette
smokers (Whittington et al., 2018). Smoke exposure especially during pregnancy and lactation is one of the
most widespread chemical insults, and thus continues to have a…

Funding

This study was funded by Deanship of Research at Jordan University of Science and Technology (grant
number 20180494). Dr. Shihadeh is supported by the National Institute on Drug Abuse of the U.S. National
Institutes of Health (NIH) and the Center for Tobacco Products of the U.S. Food and Drug Administration
(FDA) under Award Number U54DA036105. This content is solely the responsibility of the authors and does
not necessarily represent the official views of the NIH or FDA.…

Declaration of Interest

Dr. Shihdaeh is named on a patent application for a device that measures the puffing behavior of electronic
cigarette users. All other authors have no disclosures.…

CRedit authorship contribution statement

Nour Al-Sawalha: Conceptualization, Methodology, Formal analysis, Writing – Original Draft, Funding
acquisition. Roba Bdeir: Methodology, Writing – Original draft. Aiman Sohaib: Methodology, Writing –
Review & Editing. Marwan Saad: Methodology, Writing – Review & Editing. Tasneem Inghaimesh:
Methodology, Writing – Review & Editing. Omar F. Khabour: Writing – Review & Editing. Karem Alzoubi:
Writing – Review & Editing, Alan Shihadeh: Writing – Review & Editing.…

Declaration of Competing Interest

The authors declare the following financial interests/personal relationships which may be considered as
potential competing interests: Dr. Shihdaeh is named on a patent application for a device that measures the
puffing behavior of electronic cigarette users. All other authors have no disclosures.…

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