# Investigating Implications of E-Cigarettes on Pregnancy Success and Reproductive Fitness

> **NIH NIH K99** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $101,628

## Abstract

Project Summary/Abstract
 Electronic nicotinic delivery systems (ENDS) or e-cigarettes are widely used in the
nation today, despite a paucity of information regarding their safety. In particular, ENDS usage
by pregnant women is prevalent, as cigarette smoking during pregnancy is associated with
miscarriage and fetal death. However, little is known regarding the safety of ENDS use during
pregnancy. ENDS is made up of a liquid containing a mixture of propylene glycol and vegetable
glycerine with additions of flavorings, nicotine, and thickening agents that is heated, aerosolized,
and inhaled. Supplementation of ENDS with flavors and thickening agents can dramatically
enhance the toxicity level and thus, impair fine-tuned biological processes such as pregnancy.
At the start of pregnancy, the uterine stroma and epithelium communicate in a complex
orchestration of molecular and hormone signaling events to coordinate the implantation of an
embryo. After implantation, the fetal-derived trophoblast cells invade into the maternal tissue to
remodel the spiral arteries, initiating the formation of the placenta. My recently published data
was the first to describe that ENDS exposure elongated the timing of pregnancy and caused a
delay in embryo implantation. I also determined ENDS exposure elicited a dramatic
transcriptomic shift at the time of implantation. However, no studies have further examined the
mechanism causing implantation delay. ENDS exposure was identified to impair trophoblast cell
function in vitro, yet no in vivo studies have examined placental development. Although most
ENDS users enjoy the addition of flavors, no studies have examined ENDS with flavor usage or
thickening agents on pregnancy. Thus, there is an urgent need to further examine how ENDS
can influence pregnancy. This proposal aims to 1.) test how ENDS with additives affects fertility
and placental development, 2.) investigate the ENDS-driven mechanisms resulting in delayed
implantation using an in vitro human epithelial organoid model, and 3.) determine the timing and
cause of in vivo ENDS-induced delayed embryo implantation. This proposal provides a detailed
plan to examine how ENDS regulates fertility and early pregnancy success and proposes to
validate ENDS-mediated molecular mechanisms delaying implantation. This study can advise
the public on the measure of caution observed for ENDS usage in pregnancy and can expand
our understanding of mechanisms that regulate implantation success, benefitting women
experiencing infertility or recurrent implantation failure.

## Key facts

- **NIH application ID:** 10190069
- **Project number:** 1K99HD104900-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Margeaux Wetendorf Marbrey
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $101,628
- **Award type:** 1
- **Project period:** 2021-05-05 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190069

## Citation

> US National Institutes of Health, RePORTER application 10190069, Investigating Implications of E-Cigarettes on Pregnancy Success and Reproductive Fitness (1K99HD104900-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190069. Licensed CC0.

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